1B5T

ESCHERICHIA COLI METHYLENETETRAHYDROFOLATE REDUCTASE

1B5T の概要

• エントリーDOI: 10.2210/pdb1b5t/pdb
• 分子名称: PROTEIN (METHYLENETETRAHYDROFOLATE REDUCTASE), MERCURY (II) ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: beta alpha barrel, reductase, oxidoreductase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 95304.73

構造登録者

Guenther, B.D.,Sheppard, C.A.,Tran, P.,Rozen, R.,Matthews, R.G.,Ludwig, M.L. (登録日: 1999-01-07, 公開日: 1999-01-20, 最終更新日: 2024-02-07)

主引用文献

Guenther, B.D.,Sheppard, C.A.,Tran, P.,Rozen, R.,Matthews, R.G.,Ludwig, M.L.
The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia.
Nat.Struct.Biol., 6:359-365, 1999

PubMed Abstract: Elevated plasma homocysteine levels are associated with increased risk for cardiovascular disease and neural tube defects in humans. Folate treatment decreases homocysteine levels and dramatically reduces the incidence of neural tube defects. The flavoprotein methylenetetrahydrofolate reductase (MTHFR) is a likely target for these actions of folate. The most common genetic cause of mildly elevated plasma homocysteine in humans is the MTHFR polymorphism A222V (base change C677-->T). The X-ray analysis of E. coli MTHFR, reported here, provides a model for the catalytic domain that is shared by all MTHFRs. This domain is a beta8alpha8 barrel that binds FAD in a novel fashion. Ala 177, corresponding to Ala 222 in human MTHFR, is near the bottom of the barrel and distant from the FAD. The mutation A177V does not affect Km or k(cat) but instead increases the propensity for bacterial MTHFR to lose its essential flavin cofactor. Folate derivatives protect wild-type and mutant E. coli enzymes against flavin loss, and protect human MTHFR and the A222V mutant against thermal inactivation, suggesting a mechanism by which folate treatment reduces homocysteine levels.

PubMed: 10201405
DOI: 10.1038/7594

実験手法

X-RAY DIFFRACTION (2.5 Å)