4M6L
Crystal structure of human dihydrofolate reductase (DHFR) bound to NADP+ and 5,10-dideazatetrahydrofolic acid
Summary for 4M6L
| Entry DOI | 10.2210/pdb4m6l/pdb |
| Related | 4M6J 4M6K |
| Descriptor | Dihydrofolate reductase, N-(4-{2-[(6S)-2-amino-4-oxo-1,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl]ethyl}benzoyl)-L-glutamic acid, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (6 entities in total) |
| Functional Keywords | rossmann fold, nadph binding, folate binding, oxidoreductase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 22917.90 |
| Authors | Bhabha, G.,Ekiert, D.C.,Wright, P.E.,Wilson, I.A. (deposition date: 2013-08-09, release date: 2013-09-25, Last modification date: 2023-09-20) |
| Primary citation | Bhabha, G.,Ekiert, D.C.,Jennewein, M.,Zmasek, C.M.,Tuttle, L.M.,Kroon, G.,Dyson, H.J.,Godzik, A.,Wilson, I.A.,Wright, P.E. Divergent evolution of protein conformational dynamics in dihydrofolate reductase. Nat.Struct.Mol.Biol., 20:1243-1249, 2013 Cited by PubMed Abstract: Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about the evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, Escherichia coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary-sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics following a pattern of divergent evolution that is tuned by cellular environment. PubMed: 24077226DOI: 10.1038/nsmb.2676 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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