{"id":436,"date":"2015-03-17T11:25:29","date_gmt":"2015-03-17T07:25:29","guid":{"rendered":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/?page_id=436"},"modified":"2015-05-26T10:25:30","modified_gmt":"2015-05-26T06:25:30","slug":"crystal-protein-structures","status":"publish","type":"page","link":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/?page_id=436","title":{"rendered":"Protein Crystal Structures"},"content":{"rendered":"<p><!-- index.php -->\n<div\n\tclass=\"ngg-galleryoverview ngg-ajax-pagination-none\"\n\tid=\"ngg-gallery-630-1\">\n\n    \t<div class=\"slideshowlink\">\n        <a href='https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php\/nggallery\/slideshow?page_id=436'>[Slideshow]<\/a>\n\t\t\n\t<\/div>\n\t\t\t<!-- Thumbnails -->\n\t\t\t\t<div id=\"ngg-image-0\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/1_HK2_2NZT.png\"\n               title=\"&lt;b&gt;Crystal Structure of Human Hexokinase II&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2NZT\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M.&lt;\/b&gt;,  Zhu, H.,  Nedyalkova, L.,  Tempel, W.,  Wasney, G.,  Landry, R.,  Vedadi, M.,  Arrowsmith, C.H.,  Edwards, A.M.,  Sundstrom, M.,  Weigelt, J.,  Bochkarev, A.,  Park, H.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nHexokinase (HK) catalyzes the first step of glycolysis where glucose is phosphorylated to glucose-6-phosphate in the presence of ATP. The product of the HK reaction, glucose-6-phospahate, functions as feedback inhibitor. Four isoforms of hexokinase have been characterized in mammalian tissue. Among these, HK 1, 2 and 3 have a molecular mass near 100 kDa with N- and C-terminal domain. Only HK2 has catalytically active domains but HK 1 and 3 have active C-terminal domain only. HK2 is over-expressed in many cancers increasing their capacity to metabolize glucose at an elevated rate, a phenotype used clinically to detect cancer through positron emission tomography (PET) by injecting patients with 18F labeled 2-fluoro-2-deoxy-D-glucose (Holder, Jr. et al., 1998;Mathupala et al., 2006). When bound to the mitochondrial, HK2, suppresses the death of cancer cells, thus increasing the possibility for metastasis and the ultimate death of the human host.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nWe solved the structure of human hexokinase 2 (HK2) in complex with glucose and glucose-6-phosphate. HK2 appear as a dimer in the asymmetric unit even though it is monomer in solution, based on gel filtration. The monomer contains two domains, an N-terminal and a C-terminal domains. The two domains are linked by a seven turn \u03b1-helix, which is part of the N-terminal domain. The overall folding of the two domains is very similar except the N-terminal domain, which has an extra \u03b1-helix at its N-terminal end that is used to interact with the mitochondrial membrane. Each domain contains two sub-domains, a small (blue) and a large (pink) sub-domains, that sandwich the active site. The small sub-domain consists of a seven-stranded \u03b2-sheet that is surrounded by three \u03b1-helices from one side and by the large sub-domain from the other side. On the other hand, the large sub-domain consists of a six-stranded \u03b2-sheet that is surrounded by eleven \u03b1-helices of different sizes from one side and by two \u03b1-helices and the small sub-domain from the other side. One of the later two \u03b1-helices is positioned between the two sub-domains and function as a hinge to open and close the active site.\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/1_HK2_2NZT.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_1_HK2_2NZT.png\"\n               data-image-id=\"3\"\n               data-title=\"Crystal Structure of Human Hexokinase II: PDB Code 2NZT\"\n               data-description=\"&lt;b&gt;Crystal Structure of Human Hexokinase II&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2NZT\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M.&lt;\/b&gt;,  Zhu, H.,  Nedyalkova, L.,  Tempel, W.,  Wasney, G.,  Landry, R.,  Vedadi, M.,  Arrowsmith, C.H.,  Edwards, A.M.,  Sundstrom, M.,  Weigelt, J.,  Bochkarev, A.,  Park, H.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nHexokinase (HK) catalyzes the first step of glycolysis where glucose is phosphorylated to glucose-6-phosphate in the presence of ATP. The product of the HK reaction, glucose-6-phospahate, functions as feedback inhibitor. Four isoforms of hexokinase have been characterized in mammalian tissue. Among these, HK 1, 2 and 3 have a molecular mass near 100 kDa with N- and C-terminal domain. Only HK2 has catalytically active domains but HK 1 and 3 have active C-terminal domain only. HK2 is over-expressed in many cancers increasing their capacity to metabolize glucose at an elevated rate, a phenotype used clinically to detect cancer through positron emission tomography (PET) by injecting patients with 18F labeled 2-fluoro-2-deoxy-D-glucose (Holder, Jr. et al., 1998;Mathupala et al., 2006). When bound to the mitochondrial, HK2, suppresses the death of cancer cells, thus increasing the possibility for metastasis and the ultimate death of the human host.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nWe solved the structure of human hexokinase 2 (HK2) in complex with glucose and glucose-6-phosphate. HK2 appear as a dimer in the asymmetric unit even though it is monomer in solution, based on gel filtration. The monomer contains two domains, an N-terminal and a C-terminal domains. The two domains are linked by a seven turn \u03b1-helix, which is part of the N-terminal domain. The overall folding of the two domains is very similar except the N-terminal domain, which has an extra \u03b1-helix at its N-terminal end that is used to interact with the mitochondrial membrane. Each domain contains two sub-domains, a small (blue) and a large (pink) sub-domains, that sandwich the active site. The small sub-domain consists of a seven-stranded \u03b2-sheet that is surrounded by three \u03b1-helices from one side and by the large sub-domain from the other side. On the other hand, the large sub-domain consists of a six-stranded \u03b2-sheet that is surrounded by eleven \u03b1-helices of different sizes from one side and by two \u03b1-helices and the small sub-domain from the other side. One of the later two \u03b1-helices is positioned between the two sub-domains and function as a hinge to open and close the active site.\"\n               data-image-slug=\"hk2-human-hexokinase-ii\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Crystal Structure of Human Hexokinase II: PDB Code 2NZT\"\n                    alt=\"Crystal Structure of Human Hexokinase II: PDB Code 2NZT\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_1_HK2_2NZT.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-1\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/2_Septin2_2QNR.png\"\n               title=\"&lt;b&gt;Crystal Structure of Human Septin 2 in Complex with GDP&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2QNR\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh W.M.&lt;\/b\/, Nedyalkova L, Landry R, Crombet L, Kozieradzki I, Senisterra G, Vedadi M, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nSeptins, GTP-binding proteins, have been implicated in a diversity of cellular processes including cytokinesis, vesicle trafficking and exocytosis in mammalian cells (1). In humans, 13 septin genes have been identified and many of these genes undergo alternative splicing to generate additional proteins. Septins can be isolated from a cytosol as hetero-polymeric complexes. However, it is unclear how polymerization is regulated and contributes to septin function in vivo. The recent findings show that septins are associated with the pathogenesis of various diseases including neoplasia and neurodegenerative conditions (2). Septin2, the best-characterized member of the septin family, forms a complex with septin6 and septin7 in vitro (3). To understand septin function in molecular level, we solved the structure of the GTPase domain of septin2 (SEPT2) in complex with GDP.\r\nStructural features\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nA SEPT2 dimer is found in the asymmetrical unit of the crystal, consistent with the result of size-exclusion chromatography. The basic structure of each SEPT2 resembles the canonical GTPase fold of Ras proteins with six \u03b2-strands sandwiched by five \u03b1-helices. The interface of the SEPT2 dimer involves the nucleotide-binding site. There are two hydrophobic interactions in the dimerization. Phe156 of the first SEPT2 interacts with the same residue from the second molecule whereas Trp260 of the first SEPT2 interacts with Val263 and His 270 of the second molecule. The structure shows that SEPT2 dimerizes using the nucleotide-binding site with face-to-face orientation.\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/2_Septin2_2QNR.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_2_Septin2_2QNR.png\"\n               data-image-id=\"4\"\n               data-title=\"Crystal Structure of Human Septin 2 in Complex with GDP: PDB Code 2QNR\"\n               data-description=\"&lt;b&gt;Crystal Structure of Human Septin 2 in Complex with GDP&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2QNR\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh W.M.&lt;\/b\/, Nedyalkova L, Landry R, Crombet L, Kozieradzki I, Senisterra G, Vedadi M, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nSeptins, GTP-binding proteins, have been implicated in a diversity of cellular processes including cytokinesis, vesicle trafficking and exocytosis in mammalian cells (1). In humans, 13 septin genes have been identified and many of these genes undergo alternative splicing to generate additional proteins. Septins can be isolated from a cytosol as hetero-polymeric complexes. However, it is unclear how polymerization is regulated and contributes to septin function in vivo. The recent findings show that septins are associated with the pathogenesis of various diseases including neoplasia and neurodegenerative conditions (2). Septin2, the best-characterized member of the septin family, forms a complex with septin6 and septin7 in vitro (3). To understand septin function in molecular level, we solved the structure of the GTPase domain of septin2 (SEPT2) in complex with GDP.\r\nStructural features\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nA SEPT2 dimer is found in the asymmetrical unit of the crystal, consistent with the result of size-exclusion chromatography. The basic structure of each SEPT2 resembles the canonical GTPase fold of Ras proteins with six \u03b2-strands sandwiched by five \u03b1-helices. The interface of the SEPT2 dimer involves the nucleotide-binding site. There are two hydrophobic interactions in the dimerization. Phe156 of the first SEPT2 interacts with the same residue from the second molecule whereas Trp260 of the first SEPT2 interacts with Val263 and His 270 of the second molecule. The structure shows that SEPT2 dimerizes using the nucleotide-binding site with face-to-face orientation.\"\n               data-image-slug=\"septin-2-human-septin-2-in-complex-with-gdp\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Crystal Structure of Human Septin 2 in Complex with GDP: PDB Code 2QNR\"\n                    alt=\"Crystal Structure of Human Septin 2 in Complex with GDP: PDB Code 2QNR\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_2_Septin2_2QNR.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-2\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/9_ARL5_2H16.png\"\n               title=\"\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/9_ARL5_2H16.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_9_ARL5_2H16.png\"\n               data-image-id=\"11\"\n               data-title=\"ARL5: Human ADP-Ribosylation Factor-Like 5: PDB Code: 2H16 and 2H17\"\n               data-description=\"\"\n               data-image-slug=\"arl5-human-adp-ribosylation-factor-like-5\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"ARL5: Human ADP-Ribosylation Factor-Like 5: PDB Code: 2H16 and 2H17\"\n                    alt=\"ARL5: Human ADP-Ribosylation Factor-Like 5: PDB Code: 2H16 and 2H17\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_9_ARL5_2H16.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-3\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/3_NRK1_2POE.png\"\n               title=\"&lt;b&gt;Human Nicotinamide Riboside Kinase 1 in Complex with Tiazofurin&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2P0E\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nNicotinamide adenine dinucleotide (NAD+) plays important roles in the cell as a redox factor in processes such as oxidative phosphorylation and the TCA cycle and as a substrate for NAD+-consuming enzymes (Belenky et al., 2007). In addition, NAD+ can protect against neurodegeneration through the stimulation of the NRK pathway (Sasaki et al., 2006). In eukaryotes, tryptophan is the precursor of NAD+ but organisms with a low tryptophan intake can synthesize NAD+ by taking up nicotinamide riboside (NR) and converting it to NAD+ through phosphorylation and adenylylation (Bieganowski and Brenner, 2004). Nicotinamide riboside kinase (NRK) catalyzes the phosphorylation of NR, using ATP as a phosphate source, to produce nicotinamide mononucleotide (NMN). NMN is then adenylylated by NMN adenylyltransferases to produce NAD+.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nTiazofurin is an anti-tumor agent that is converted to the NAD+ analog, tiazofurin adenine dinucleotide (TAD+). Tiazofurin, which has overall structural similarity to NR, is phosphorylated by NRK with high specificity (Bieganowski et al., 2004). TAD+ then acts as a potent inhibitor of inosine monophosphate dehydrogenase (Carney et al., 1985). Inhibition of the latter enzyme lowers the levels of intracellular guanosine nucleotides that are essential for tumor cell growth and replication (Carney et al., 1985).\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/3_NRK1_2POE.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_3_NRK1_2POE.png\"\n               data-image-id=\"5\"\n               data-title=\"Human Nicotinamide Riboside Kinase 1 in Complex with Tiazofurin: PDB Code: 2P0E\"\n               data-description=\"&lt;b&gt;Human Nicotinamide Riboside Kinase 1 in Complex with Tiazofurin&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2P0E\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nNicotinamide adenine dinucleotide (NAD+) plays important roles in the cell as a redox factor in processes such as oxidative phosphorylation and the TCA cycle and as a substrate for NAD+-consuming enzymes (Belenky et al., 2007). In addition, NAD+ can protect against neurodegeneration through the stimulation of the NRK pathway (Sasaki et al., 2006). In eukaryotes, tryptophan is the precursor of NAD+ but organisms with a low tryptophan intake can synthesize NAD+ by taking up nicotinamide riboside (NR) and converting it to NAD+ through phosphorylation and adenylylation (Bieganowski and Brenner, 2004). Nicotinamide riboside kinase (NRK) catalyzes the phosphorylation of NR, using ATP as a phosphate source, to produce nicotinamide mononucleotide (NMN). NMN is then adenylylated by NMN adenylyltransferases to produce NAD+.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nTiazofurin is an anti-tumor agent that is converted to the NAD+ analog, tiazofurin adenine dinucleotide (TAD+). Tiazofurin, which has overall structural similarity to NR, is phosphorylated by NRK with high specificity (Bieganowski et al., 2004). TAD+ then acts as a potent inhibitor of inosine monophosphate dehydrogenase (Carney et al., 1985). Inhibition of the latter enzyme lowers the levels of intracellular guanosine nucleotides that are essential for tumor cell growth and replication (Carney et al., 1985).\"\n               data-image-slug=\"nrk-1-human-nicotinamide-riboside-kinase-1-in-complex-with-tiazofurin\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Human Nicotinamide Riboside Kinase 1 in Complex with Tiazofurin: PDB Code: 2P0E\"\n                    alt=\"Human Nicotinamide Riboside Kinase 1 in Complex with Tiazofurin: PDB Code: 2P0E\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_3_NRK1_2POE.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-4\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/4_CK_2GL6.png\"\n               title=\"&lt;b&gt;Crystal Structure of Human Creatine Kinase, Mitochondrial 2 (sarcomeric)&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2GL6\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nCreatine kinase (CK) catalyzes the reversible transfer of a phosphoryl group from MgATP to creatine producing phosphocreatine and MgADP, where the phosphoryl transfer was found to be the rate-limiting step1. CK is highly expressed in rapidly respiring tissues, including smooth and striated muscle, heart muscle, brain, sperm and mitochondria. Four CK isozymes exist in the cell. There are two cytosolic forms, the muscle and brain forms, which exist as dimers under physiological conditions, and two mitochondrial forms, the ubiquitous and sarcomeric forms, which generally exist as octamers but can be dissociated into dimers2. The reaction rates of the mitochondrial isozymes are generally 3 to 4 times slower than their cytosolic counterparts, and the reverse reaction is always faster than the forward reaction3. \r\n&lt;br&gt;\r\n&lt;br&gt;\r\nCK was known for its function in maintaining steady energy levels at sites of high energy turnover, where it buffer the cell against rapid depletion of ATP by the interconversion of phosphocreatine and ADP to creatine and ATP 3. Here we report the structure of the human octomeric form of mitochondrial creatine kinase from sarcomere in complex with MgADP. The structure provides insight into the catalytic mechanism of creatine kinase.\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/4_CK_2GL6.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_4_CK_2GL6.png\"\n               data-image-id=\"6\"\n               data-title=\"Crystal Structure of Human Creatine Kinase, Mitochondrial 2 (sarcomeric): PDB Code: 2GL6\"\n               data-description=\"&lt;b&gt;Crystal Structure of Human Creatine Kinase, Mitochondrial 2 (sarcomeric)&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2GL6\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nCreatine kinase (CK) catalyzes the reversible transfer of a phosphoryl group from MgATP to creatine producing phosphocreatine and MgADP, where the phosphoryl transfer was found to be the rate-limiting step1. CK is highly expressed in rapidly respiring tissues, including smooth and striated muscle, heart muscle, brain, sperm and mitochondria. Four CK isozymes exist in the cell. There are two cytosolic forms, the muscle and brain forms, which exist as dimers under physiological conditions, and two mitochondrial forms, the ubiquitous and sarcomeric forms, which generally exist as octamers but can be dissociated into dimers2. The reaction rates of the mitochondrial isozymes are generally 3 to 4 times slower than their cytosolic counterparts, and the reverse reaction is always faster than the forward reaction3. \r\n&lt;br&gt;\r\n&lt;br&gt;\r\nCK was known for its function in maintaining steady energy levels at sites of high energy turnover, where it buffer the cell against rapid depletion of ATP by the interconversion of phosphocreatine and ADP to creatine and ATP 3. Here we report the structure of the human octomeric form of mitochondrial creatine kinase from sarcomere in complex with MgADP. The structure provides insight into the catalytic mechanism of creatine kinase.\"\n               data-image-slug=\"ck-human-mitochondrial-creatine-kinase\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Crystal Structure of Human Creatine Kinase, Mitochondrial 2 (sarcomeric): PDB Code: 2GL6\"\n                    alt=\"Crystal Structure of Human Creatine Kinase, Mitochondrial 2 (sarcomeric): PDB Code: 2GL6\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_4_CK_2GL6.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-5\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/5_ChKa_2I7Q.png\"\n               title=\"&lt;b&gt;Crystal Structure of Human Choline Kinase \u03b1&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 271Q\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nPhospholipids play a role as a source of lipid molecules and a structural role in membranes by creating the milieu in which membrane proteins function. Eukaryotic cell membranes contain many different phospholipid species with the most abundant one being phosphatidylcholine (PC), which is synthesized through the CDP-choline pathway, also known as the Kennedy pathway. Initially, choline is imported into the cell and is rapidly converted to phosphocholine by choline kinase.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nIn humans, two choline kinase genes have been found: CHKA and CHKB. ChKa is the most abundant in testis and liver whereas CHKB is ubiquitous. ChK is a homodimer (A\/A or B\/B) as well as a heterodimer (A\/B). Alterations in phospholipids metabolism are linked to programmed cell death and oncogenic transformation. Increased CHK activity and elevated phosphocholine levels have been found in human cancer cells, suggesting that the up regulation of CHK participates in the generation of human tumors. Therefore, ChK isoforms may be potential targets for anticancer drug discovery.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nWe have solved the structure of the apo-choline kinase ChKa and ChKb, both of which consist of a mixed \u03b1\/\u03b2 fold. The overall fold of choline kinase A and B is similar to the actin fold. Choline kinase a and a were both found to be homodimeric in solution and in the crystal lattice. Each monomer contains small and large domains (ChKa, ChKb) and the putative active site is located between the two domains, and is highly conserved in both isozymes. The small domain of ChKa contains five-stranded antiparallel \u03b2-sheet surrounded by two \u03b1-helices from each side. The large domain ChKa contains mainly \u03b1-helices and four \u03b2-sheets: seven long \u03b1-helices and four single turn \u03b1-helices construct the large domain along with two double-stranded \u03b2-sheets. The linker region of the two domains is a three-stranded antiparallel \u03b2-sheet. The dimer is formed through interactions between the small domain of one monomer and the large domain of the other monomer.\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/5_ChKa_2I7Q.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_5_ChKa_2I7Q.png\"\n               data-image-id=\"7\"\n               data-title=\"Crystal Structure of Human Choline Kinase \u03b1: PDB Code: 271Q\"\n               data-description=\"&lt;b&gt;Crystal Structure of Human Choline Kinase \u03b1&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 271Q\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nPhospholipids play a role as a source of lipid molecules and a structural role in membranes by creating the milieu in which membrane proteins function. Eukaryotic cell membranes contain many different phospholipid species with the most abundant one being phosphatidylcholine (PC), which is synthesized through the CDP-choline pathway, also known as the Kennedy pathway. Initially, choline is imported into the cell and is rapidly converted to phosphocholine by choline kinase.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nIn humans, two choline kinase genes have been found: CHKA and CHKB. ChKa is the most abundant in testis and liver whereas CHKB is ubiquitous. ChK is a homodimer (A\/A or B\/B) as well as a heterodimer (A\/B). Alterations in phospholipids metabolism are linked to programmed cell death and oncogenic transformation. Increased CHK activity and elevated phosphocholine levels have been found in human cancer cells, suggesting that the up regulation of CHK participates in the generation of human tumors. Therefore, ChK isoforms may be potential targets for anticancer drug discovery.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nWe have solved the structure of the apo-choline kinase ChKa and ChKb, both of which consist of a mixed \u03b1\/\u03b2 fold. The overall fold of choline kinase A and B is similar to the actin fold. Choline kinase a and a were both found to be homodimeric in solution and in the crystal lattice. Each monomer contains small and large domains (ChKa, ChKb) and the putative active site is located between the two domains, and is highly conserved in both isozymes. The small domain of ChKa contains five-stranded antiparallel \u03b2-sheet surrounded by two \u03b1-helices from each side. The large domain ChKa contains mainly \u03b1-helices and four \u03b2-sheets: seven long \u03b1-helices and four single turn \u03b1-helices construct the large domain along with two double-stranded \u03b2-sheets. The linker region of the two domains is a three-stranded antiparallel \u03b2-sheet. The dimer is formed through interactions between the small domain of one monomer and the large domain of the other monomer.\"\n               data-image-slug=\"5_chka_2i7q-png-1\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Crystal Structure of Human Choline Kinase \u03b1: PDB Code: 271Q\"\n                    alt=\"Crystal Structure of Human Choline Kinase \u03b1: PDB Code: 271Q\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_5_ChKa_2I7Q.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-6\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/6_ChKb_2IG7.png\"\n               title=\"&lt;b&gt;Crystal structure of human choline kinase \u03b2&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2IG7\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nPhospholipids play a role as a source of lipid molecules and a structural role in membranes by creating the milieu in which membrane proteins function. Eukaryotic cell membranes contain many different phospholipid species with the most abundant one being phosphatidylcholine (PC), which is synthesized through the CDP-choline pathway, also known as the Kennedy pathway. Initially, choline is imported into the cell and is rapidly converted to phosphocholine by choline kinase.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nIn humans, two choline kinase genes have been found: CHKA and CHKB. ChKa is the most abundant in testis and liver whereas CHKB is ubiquitous. ChK is a homodimer (A\/A or B\/B) as well as a heterodimer (A\/B). Alterations in phospholipids metabolism are linked to programmed cell death and oncogenic transformation. Increased CHK activity and elevated phosphocholine levels have been found in human cancer cells, suggesting that the up regulation of CHK participates in the generation of human tumors. Therefore, ChK isoforms may be potential targets for anticancer drug discovery.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nWe have solved the structure of the apo-choline kinase ChKa and ChKb, both of which consist of a mixed \u03b1\/\u03b2 fold. The overall fold of choline kinase A and B is similar to the actin fold. Choline kinase a and a were both found to be homodimeric in solution and in the crystal lattice. Each monomer contains small and large domains (ChKa, ChKb) and the putative active site is located between the two domains, and is highly conserved in both isozymes. The small domain of ChKa contains five-stranded antiparallel \u03b2-sheet surrounded by two \u03b1-helices from each side. The large domain ChKa contains mainly \u03b1-helices and four \u03b2-sheets: seven long \u03b1-helices and four single turn \u03b1-helices construct the large domain along with two double-stranded \u03b2-sheets. The linker region of the two domains is a three-stranded antiparallel \u03b2-sheet. The dimer is formed through interactions between the small domain of one monomer and the large domain of the other monomer.\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/6_ChKb_2IG7.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_6_ChKb_2IG7.png\"\n               data-image-id=\"8\"\n               data-title=\"Crystal structure of human choline kinase \u03b2: PDB Code: 2IG7\"\n               data-description=\"&lt;b&gt;Crystal structure of human choline kinase \u03b2&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2IG7\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nPhospholipids play a role as a source of lipid molecules and a structural role in membranes by creating the milieu in which membrane proteins function. Eukaryotic cell membranes contain many different phospholipid species with the most abundant one being phosphatidylcholine (PC), which is synthesized through the CDP-choline pathway, also known as the Kennedy pathway. Initially, choline is imported into the cell and is rapidly converted to phosphocholine by choline kinase.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nIn humans, two choline kinase genes have been found: CHKA and CHKB. ChKa is the most abundant in testis and liver whereas CHKB is ubiquitous. ChK is a homodimer (A\/A or B\/B) as well as a heterodimer (A\/B). Alterations in phospholipids metabolism are linked to programmed cell death and oncogenic transformation. Increased CHK activity and elevated phosphocholine levels have been found in human cancer cells, suggesting that the up regulation of CHK participates in the generation of human tumors. Therefore, ChK isoforms may be potential targets for anticancer drug discovery.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nWe have solved the structure of the apo-choline kinase ChKa and ChKb, both of which consist of a mixed \u03b1\/\u03b2 fold. The overall fold of choline kinase A and B is similar to the actin fold. Choline kinase a and a were both found to be homodimeric in solution and in the crystal lattice. Each monomer contains small and large domains (ChKa, ChKb) and the putative active site is located between the two domains, and is highly conserved in both isozymes. The small domain of ChKa contains five-stranded antiparallel \u03b2-sheet surrounded by two \u03b1-helices from each side. The large domain ChKa contains mainly \u03b1-helices and four \u03b2-sheets: seven long \u03b1-helices and four single turn \u03b1-helices construct the large domain along with two double-stranded \u03b2-sheets. The linker region of the two domains is a three-stranded antiparallel \u03b2-sheet. The dimer is formed through interactions between the small domain of one monomer and the large domain of the other monomer.\"\n               data-image-slug=\"6_chkb_2ig7-png-1\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Crystal structure of human choline kinase \u03b2: PDB Code: 2IG7\"\n                    alt=\"Crystal structure of human choline kinase \u03b2: PDB Code: 2IG7\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_6_ChKb_2IG7.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-7\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/7_RK_2FV7.png\"\n               title=\"&lt;b&gt;Human Ribokinase&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2FV7\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nSugars are used by cells as a source of energy or carbon. The first step in sugar metabolism after transport into the cell is phosphorylation, which is catalyzed by specific sugar kinases. Sugars phosphorylation will trap them inside the cell to prepare for use in the synthesis of nucleotides, tryptophan and histidine or as a component of the pentose phosphate pathway. The kinetic mechanisms of sugar kinases are similar, where the sugar hydroxyl oxygen functions as a nucleophile and ATP as a phosphate donor. The reaction requires divalent metal ion, which functions as an electrophilic catalyst to aid phosphoryl group transfer1. Divalent cations also neutralize the negative charges of the nucleotide, and accommodate the \u03b3-phosphate of ATP in a favorable conformation for the reaction to take place1.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nRibose is one of the key sugars in the cell, and before entering the metabolic pathways, ribose must first be phosphorylated. Ribokinase (RK, EC 2.7.1.15), or ATP:D-ribose 5-phosphotransferase, is a carbohydrate kinase which catalyzes the phosphorylation of ribose to ribose 5-phosphate in a reaction that requires ATP and magnesium2. Here we report the structure of human-ribokinase bound to ADP and magnesium. The structure will give insight into the catalytic mechanism of ribokinase.\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/7_RK_2FV7.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_7_RK_2FV7.png\"\n               data-image-id=\"9\"\n               data-title=\"Human Ribokinase: PDB Code: 2FV7\"\n               data-description=\"&lt;b&gt;Human Ribokinase&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2FV7\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nSugars are used by cells as a source of energy or carbon. The first step in sugar metabolism after transport into the cell is phosphorylation, which is catalyzed by specific sugar kinases. Sugars phosphorylation will trap them inside the cell to prepare for use in the synthesis of nucleotides, tryptophan and histidine or as a component of the pentose phosphate pathway. The kinetic mechanisms of sugar kinases are similar, where the sugar hydroxyl oxygen functions as a nucleophile and ATP as a phosphate donor. The reaction requires divalent metal ion, which functions as an electrophilic catalyst to aid phosphoryl group transfer1. Divalent cations also neutralize the negative charges of the nucleotide, and accommodate the \u03b3-phosphate of ATP in a favorable conformation for the reaction to take place1.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nRibose is one of the key sugars in the cell, and before entering the metabolic pathways, ribose must first be phosphorylated. Ribokinase (RK, EC 2.7.1.15), or ATP:D-ribose 5-phosphotransferase, is a carbohydrate kinase which catalyzes the phosphorylation of ribose to ribose 5-phosphate in a reaction that requires ATP and magnesium2. Here we report the structure of human-ribokinase bound to ADP and magnesium. The structure will give insight into the catalytic mechanism of ribokinase.\"\n               data-image-slug=\"rk-human-ribokinase\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Human Ribokinase: PDB Code: 2FV7\"\n                    alt=\"Human Ribokinase: PDB Code: 2FV7\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_7_RK_2FV7.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-8\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/8_PAPSS2_2AX4.png\"\n               title=\"&lt;b&gt;Human ATP Kinase Domain of 3\u2019-Phosphoadenosine-5\u2019-Phosphosulfate&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2AX4\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M.&lt;\/b&gt;,  Nedyalkova, L.,  Ismail, S.,  Park, H.,  Arrowsmith, C.,  Edwards, A.,  Sundstrom, M.,  Weigelt, J.,  Bochkarev, A.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nSulfation is an essential process for normal growth and development. First, sulfate is actively transferred into the cell where it is converted into the high energy compound 3\u2019-phosphoadenosine-5\u2019-phosphosulfate (PAPS) which then functions as a sulfate donor via a multitude of sulfotransferases. In human, PAPS synthetase (hPAPSS) is a bi-functional enzyme catalyzing two subsequent reactions using ATP and sulfate.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nThe ATP sulfurylase domain forms adenosine-5\u2019-phosphosulfate (APS), which is then phosphorylated by the APS kinase domain to yield PAPS. The high energy sulfate donor PAPS is involved in sulfate conjugation of several substrates including extracellular matrix, hormones and drugs. A decrease in PAPS synthesis leads to severe developmental defects in human skeletons.1In humans, PAPSS has two isozymes with 77% identity at the amino acid level. Human PAPSS-1 is ubiquitously expressed and is the dominant isoform in most tissues, whereas expression of the PAPSS-2 is variable and tissue-specific.2 Here we present the crystal structure of the APS kinase domain of hPAPSS-2 at 2.5 \u00c5 resolution a homodimer with ADP bound.\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/8_PAPSS2_2AX4.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_8_PAPSS2_2AX4.png\"\n               data-image-id=\"10\"\n               data-title=\"Human ATP Kinase Domain of 3\u2019-Phosphoadenosine-5\u2019-Phosphosulfate: PDB Code: 2AX4\"\n               data-description=\"&lt;b&gt;Human ATP Kinase Domain of 3\u2019-Phosphoadenosine-5\u2019-Phosphosulfate&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2AX4\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M.&lt;\/b&gt;,  Nedyalkova, L.,  Ismail, S.,  Park, H.,  Arrowsmith, C.,  Edwards, A.,  Sundstrom, M.,  Weigelt, J.,  Bochkarev, A.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nSulfation is an essential process for normal growth and development. First, sulfate is actively transferred into the cell where it is converted into the high energy compound 3\u2019-phosphoadenosine-5\u2019-phosphosulfate (PAPS) which then functions as a sulfate donor via a multitude of sulfotransferases. In human, PAPS synthetase (hPAPSS) is a bi-functional enzyme catalyzing two subsequent reactions using ATP and sulfate.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nThe ATP sulfurylase domain forms adenosine-5\u2019-phosphosulfate (APS), which is then phosphorylated by the APS kinase domain to yield PAPS. The high energy sulfate donor PAPS is involved in sulfate conjugation of several substrates including extracellular matrix, hormones and drugs. A decrease in PAPS synthesis leads to severe developmental defects in human skeletons.1In humans, PAPSS has two isozymes with 77% identity at the amino acid level. Human PAPSS-1 is ubiquitously expressed and is the dominant isoform in most tissues, whereas expression of the PAPSS-2 is variable and tissue-specific.2 Here we present the crystal structure of the APS kinase domain of hPAPSS-2 at 2.5 \u00c5 resolution a homodimer with ADP bound.\"\n               data-image-slug=\"papss2-human-3-phosphoadenosine-5-phosphosulfate\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Human ATP Kinase Domain of 3\u2019-Phosphoadenosine-5\u2019-Phosphosulfate: PDB Code: 2AX4\"\n                    alt=\"Human ATP Kinase Domain of 3\u2019-Phosphoadenosine-5\u2019-Phosphosulfate: PDB Code: 2AX4\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_8_PAPSS2_2AX4.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-9\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/9_ARL5_2H17.png\"\n               title=\"&lt;b&gt;Human ADP-Ribosylation Factor-Like 5 Isoform 1&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2H16 and 2H17\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M.&lt;\/b&gt;search; Tempel, W.search; Yaniw, D.search; Arrowsmith, C.H.search; Edwards, A.M.search; Sundstrom, M.search; Weigelt, J.search; Bochkarev, A.search; Park, H.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nADP-ribosylation factor-like 5 (ARL5) belongs to the ARF family of GTP-binding proteins. The cellular function of ARL5 is currently unknown. The primary sequence of ARL5 is most similar to that of ADP-ribosylation factor-like 8 (ARL8), which is potentially involved in brain development. Here, we solved the structure of the complex of ARL5 with GDP. The ARL5-GDP structure is similar to our recent ARL8-GDP structure (PDB code 1YZG) as expected from their sequence similarity. Particularly the N-terminal helix forms hydrophobic interactions with the main body of ARL5. This N-terminal helix binding site of ARL5 is located opposite from the GTP\/GDP binding site. Based on the membrane recruitment mechanism of the ARF family proteins, the N-terminal helix will be displaced to interact with membranes when GTP replaces GDP. Although the ARL5-GTP structure is not known, we hypothesize that the hydrophobic side chains of the N-terminal helix of ARL5 will be responsible for the interactions with membranes. Further studies will be necessary to prove this hypothesis.\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/9_ARL5_2H17.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_9_ARL5_2H17.png\"\n               data-image-id=\"12\"\n               data-title=\"Human ADP-Ribosylation Factor-Like 5 Isoform 1: PDB Code: 2H16 and 2H17\"\n               data-description=\"&lt;b&gt;Human ADP-Ribosylation Factor-Like 5 Isoform 1&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2H16 and 2H17\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M.&lt;\/b&gt;search; Tempel, W.search; Yaniw, D.search; Arrowsmith, C.H.search; Edwards, A.M.search; Sundstrom, M.search; Weigelt, J.search; Bochkarev, A.search; Park, H.\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nADP-ribosylation factor-like 5 (ARL5) belongs to the ARF family of GTP-binding proteins. The cellular function of ARL5 is currently unknown. The primary sequence of ARL5 is most similar to that of ADP-ribosylation factor-like 8 (ARL8), which is potentially involved in brain development. Here, we solved the structure of the complex of ARL5 with GDP. The ARL5-GDP structure is similar to our recent ARL8-GDP structure (PDB code 1YZG) as expected from their sequence similarity. Particularly the N-terminal helix forms hydrophobic interactions with the main body of ARL5. This N-terminal helix binding site of ARL5 is located opposite from the GTP\/GDP binding site. Based on the membrane recruitment mechanism of the ARF family proteins, the N-terminal helix will be displaced to interact with membranes when GTP replaces GDP. Although the ARL5-GTP structure is not known, we hypothesize that the hydrophobic side chains of the N-terminal helix of ARL5 will be responsible for the interactions with membranes. Further studies will be necessary to prove this hypothesis.\"\n               data-image-slug=\"9_arl5_2h17-png-1\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Human ADP-Ribosylation Factor-Like 5 Isoform 1: PDB Code: 2H16 and 2H17\"\n                    alt=\"Human ADP-Ribosylation Factor-Like 5 Isoform 1: PDB Code: 2H16 and 2H17\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_9_ARL5_2H17.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\t\t<div id=\"ngg-image-10\" class=\"ngg-gallery-thumbnail-box\" >\n\t\t\t\t        <div class=\"ngg-gallery-thumbnail\">\n            <a href=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/10_KHK_2HLZ.png\"\n               title=\"&lt;b&gt;Crystal Structure of Human Ketohexokinase&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2HLZ\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nFructose is metabolized through two pathways. First, the fructose 1-phosphate pathway, which utilizes the majority of fructose in the liver and kidney through the action of ketohexokinase, aldolases-B (fructose-1-phosphate aldolase) and triokinase [1]. The majority of fructose is metabolized to yield a glycolytic intermediate, glyceraldehyde-3-phosphate, which can be fed into glycolysis. The second fructose metabolism pathway is the fructose 6-phosphate pathway, which utilizes fructose via the action of hexokinase in tissues such as the small intestine, adipose, and muscle [1].\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nKetohexokinase (KHK; EC 2.7.1.3), also called fructokinase, catalyzes the phosphorylation of fructose to fructose 1-phosphate. Two missense mutations of KHK, G40R and A43T, are known.to cause fructosuria, which is characterized by a symptom of a raised blood fructose concentration after ingestion of fructose, sucrose, or sorbitol [2]. Here we report the structure of human apo-KHK. KHK is a homodimer with the molecular weight of 32.7 kDa for each monomer. The monomer has a large central domain with an alpha\/beta fold and a small domain of a 4-stranded anti-parallel beta-sheet. The dimer interface is formed by the small domains. The mutations found in fructosuria patients are located between the large and small domains. We speculate that the mutations may hinder the opening and closing of the active site, decreasing the KHK activity.\"\n               data-src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/10_KHK_2HLZ.png\"\n               data-thumbnail=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_10_KHK_2HLZ.png\"\n               data-image-id=\"13\"\n               data-title=\"Crystal Structure of Human Ketohexokinase: PDB Code: 2HLZ\"\n               data-description=\"&lt;b&gt;Crystal Structure of Human Ketohexokinase&lt;\/b&gt;\r\n&lt;br&gt;PDB Code: 2HLZ\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nAuthors: &lt;b&gt;Rabeh, W.M&lt;\/b&gt;; Tempel, W.; Nedyalkova L, Landry R, Arrowsmith CH, Edwards AM, Sundstrom M, Weigelt J, Bochkarev A, Park H\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nFructose is metabolized through two pathways. First, the fructose 1-phosphate pathway, which utilizes the majority of fructose in the liver and kidney through the action of ketohexokinase, aldolases-B (fructose-1-phosphate aldolase) and triokinase [1]. The majority of fructose is metabolized to yield a glycolytic intermediate, glyceraldehyde-3-phosphate, which can be fed into glycolysis. The second fructose metabolism pathway is the fructose 6-phosphate pathway, which utilizes fructose via the action of hexokinase in tissues such as the small intestine, adipose, and muscle [1].\r\n&lt;br&gt;\r\n&lt;br&gt;\r\nKetohexokinase (KHK; EC 2.7.1.3), also called fructokinase, catalyzes the phosphorylation of fructose to fructose 1-phosphate. Two missense mutations of KHK, G40R and A43T, are known.to cause fructosuria, which is characterized by a symptom of a raised blood fructose concentration after ingestion of fructose, sucrose, or sorbitol [2]. Here we report the structure of human apo-KHK. KHK is a homodimer with the molecular weight of 32.7 kDa for each monomer. The monomer has a large central domain with an alpha\/beta fold and a small domain of a 4-stranded anti-parallel beta-sheet. The dimer interface is formed by the small domains. The mutations found in fructosuria patients are located between the large and small domains. We speculate that the mutations may hinder the opening and closing of the active site, decreasing the KHK activity.\"\n               data-image-slug=\"10_khk_2hlz-png\"\n               class=\"ngg-fancybox\" rel=\"630\">\n                <img\n                    title=\"Crystal Structure of Human Ketohexokinase: PDB Code: 2HLZ\"\n                    alt=\"Crystal Structure of Human Ketohexokinase: PDB Code: 2HLZ\"\n                    src=\"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/wp-content\/gallery\/protein-crystal-structures\/thumbs\/thumbs_10_KHK_2HLZ.png\"\n                    width=\"300\"\n                    height=\"160\"\n                    style=\"max-width:100%;\"\n                \/>\n            <\/a>\n        <\/div>\n\t\t\t\t\t\t\t<\/div> \n\t\t\t\n        \n\t\t\n\t\t<!-- Pagination -->\n\t<div class='ngg-clear'><\/div>\t<\/div>\n<\/p>\n","protected":false},"excerpt":{"rendered":"<p>[Slideshow]<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":186,"menu_order":0,"comment_status":"open","ping_status":"open","template":"gallery-3-cols.php","meta":{"ngg_post_thumbnail":0,"footnotes":""},"class_list":["post-436","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php?rest_route=\/wp\/v2\/pages\/436","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=436"}],"version-history":[{"count":19,"href":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php?rest_route=\/wp\/v2\/pages\/436\/revisions"}],"predecessor-version":[{"id":631,"href":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php?rest_route=\/wp\/v2\/pages\/436\/revisions\/631"}],"up":[{"embeddable":true,"href":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php?rest_route=\/wp\/v2\/pages\/186"}],"wp:attachment":[{"href":"https:\/\/sites.nyuad.nyu.edu\/rabeh-lab\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=436"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}