4M6J

Crystal structure of human dihydrofolate reductase (DHFR) bound to NADPH

Summary for 4M6J

• Entry DOI: 10.2210/pdb4m6j/pdb
• Related: 4M6K 4M6L
• Descriptor: Dihydrofolate reductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 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: 22226.14

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

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: 24077226
DOI: 10.1038/nsmb.2676

Experimental method

X-RAY DIFFRACTION (1.201 Å)