5n6c | pdb_00005n6c

Crystal structure of human 3-phosphoglycerate dehydrogenase in complex with NAD and L-Tartrate

spinqualitylabelsall models 5n6c, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5n6c is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAD, TLA Gene: PHGDH, PGDH3 (HUMAN) Activity: Phosphoglycerate dehydrogenase, with EC number 1.1.1.95 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [SERA_HUMAN] Defects in PHGDH are the cause of phosphoglycerate dehydrogenase deficiency (PHGDH deficiency) [MIM:601815]. It is characterized by congenital microcephaly, psychomotor retardation, and seizures. Publication Abstract from PubMed Cancer cells reprogram their metabolism and energy production to sustain increased growth, enable metastasis and overcome resistance to cancer treatments. Although primary roles for many metabolic proteins have been identified, some are promiscuous in regards to the reaction they catalyze. To efficiently target these enzymes, a good understanding of their enzymatic function and structure, as well as knowledge regarding any substrate or catalytic promiscuity is required. Here we focus on the characterization of human 3-phosphoglycerate dehydrogenase (PHGDH). PHGDH catalyzes the NAD(+)-dependent conversion of 3-phosphoglycerate to phosphohydroxypyruvate, which is the first step in the de novo synthesis pathway of serine, a critical amino acid for protein and nucleic acid biosynthesis. We have investigated substrate analogues to assess whether PHGDH might possess other enzymatic roles that could explain its occasional over-expression in cancer, as well as to help with the design of specific inhibitors. We also report the crystal structure of the catalytic subunit of human PHGDH, a dimer, solved with bound cofactor in one monomer and both cofactor and L-tartrate in the second monomer. In vitro enzyme activity measurements show that the catalytic subunit of PHGDH is still active and that PHGDH activity could be significantly inhibited with adenosine 5'-diphosphoribose. Structural insights into the enzymatic activity and potential substrate promiscuity of human 3-phosphoglycerate dehydrogenase (PHGDH).,Unterlass JE, Wood RJ, Basle A, Tucker J, Cano C, Noble MME, Curtin NJ Oncotarget. 2017 Nov 6;8(61):104478-104491. doi: 10.18632/oncotarget.22327., eCollection 2017 Nov 28. PMID:29262655 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoglycerate dehydrogenase

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