3BQF

Structure of the central domain (MsrA) of Neisseria meningitidis PilB (complex with a substrate)

3BQF の概要

• エントリーDOI: 10.2210/pdb3bqf/pdb
• 関連するPDBエントリー: 3BQE 3BQG 3BQH
• 分子名称: Peptide methionine sulfoxide reductase msrA/msrB, (2S)-2-(acetylamino)-N-methyl-4-[(S)-methylsulfinyl]butanamide (3 entities in total)
• 機能のキーワード: pilb, methionine sulfoxide reductase a, complex with a substrate, electron transport, multifunctional enzyme, oxidoreductase, redox-active center, transport
• 由来する生物種: Neisseria meningitidis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22128.55

構造登録者

Ranaivoson, F.M.,Kauffmann, B.,Favier, F. (登録日: 2007-12-20, 公開日: 2008-02-19, 最終更新日: 2023-11-01)

主引用文献

Ranaivoson, F.M.,Antoine, M.,Kauffmann, B.,Boschi-Muller, S.,Aubry, A.,Branlant, G.,Favier, F.
A structural analysis of the catalytic mechanism of methionine sulfoxide reductase A from Neisseria meningitidis
J.Mol.Biol., 377:268-280, 2008

PubMed Abstract: The methionine sulfoxide reductases (Msrs) are thioredoxin-dependent oxidoreductases that catalyse the reduction of the sulfoxide function of the oxidized methionine residues. These enzymes have been shown to regulate the life span of a wide range of microbial and animal species and to play the role of physiological virulence determinant of some bacterial pathogens. Two structurally unrelated classes of Msrs exist, MsrA and MsrB, with opposite stereoselectivity towards the R and S isomers of the sulfoxide function, respectively. Both Msrs share a similar three-step chemical mechanism including (1) the formation of a sulfenic acid intermediate on the catalytic Cys with the concomitant release of the product-methionine, (2) the formation of an intramonomeric disulfide bridge between the catalytic and the regenerating Cys and (3) the reduction of the disulfide bridge by thioredoxin or its homologues. In this study, four structures of the MsrA domain of the PilB protein from Neisseria meningitidis, representative of four catalytic intermediates of the MsrA catalytic cycle, were determined by X-ray crystallography: the free reduced form, the Michaelis-like complex, the sulfenic acid intermediate and the disulfide oxidized forms. They reveal a conserved overall structure up to the formation of the sulfenic acid intermediate, while a large conformational switch is observed in the oxidized form. The results are discussed in relation to those proposed from enzymatic, NMR and theoretical chemistry studies. In particular, the substrate specificity and binding, the catalytic scenario of the reductase step and the relevance and role of the large conformational change observed in the oxidized form are discussed.

PubMed: 18255097
DOI: 10.1016/j.jmb.2008.01.021

実験手法

X-RAY DIFFRACTION (2.24 Å)