5N6C
Crystal structure of human 3-phosphoglycerate dehydrogenase in complex with NAD and L-Tartrate
Summary for 5N6C
| Entry DOI | 10.2210/pdb5n6c/pdb |
| Descriptor | D-3-phosphoglycerate dehydrogenase, L(+)-TARTARIC ACID, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total) |
| Functional Keywords | dehydrogenase, serine metabolism, enzymology, oxidoreductase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 65788.90 |
| Authors | Unterlass, J.E.,Basle, A.,Tucker, J.,Cano, C.,Noble, M.E.M.,Curtin, N.J. (deposition date: 2017-02-14, release date: 2017-11-22, Last modification date: 2024-01-17) |
| Primary citation | Unterlass, J.E.,Wood, R.J.,Basle, A.,Tucker, J.,Cano, C.,Noble, M.M.E.,Curtin, N.J. Structural insights into the enzymatic activity and potential substrate promiscuity of human 3-phosphoglycerate dehydrogenase (PHGDH). Oncotarget, 8:104478-104491, 2017 Cited by PubMed Abstract: 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 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 -tartrate in the second monomer. 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. PubMed: 29262655DOI: 10.18632/oncotarget.22327 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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