4M6L

Crystal structure of human dihydrofolate reductase (DHFR) bound to NADP+ and 5,10-dideazatetrahydrofolic acid

4M6L の概要

• エントリーDOI: 10.2210/pdb4m6l/pdb
• 関連するPDBエントリー: 4M6J 4M6K
• 分子名称: 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)
• 機能のキーワード: rossmann fold, nadph binding, folate binding, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22917.90

構造登録者

Bhabha, G.,Ekiert, D.C.,Wright, P.E.,Wilson, I.A. (登録日: 2013-08-09, 公開日: 2013-09-25, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.7 Å)