7APR

Bacillithiol Disulfide Reductase Bdr (YpdA) from Staphylococcus aureus

7APR の概要

• エントリーDOI: 10.2210/pdb7apr/pdb
• 関連するPDBエントリー: 7A76 7A7B
• 分子名称: YpdA family putative bacillithiol disulfide reductase Bdr, FLAVIN-ADENINE DINUCLEOTIDE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: disulfide reductase, fad, flavoprotein, nadph, oxidoreductase
• 由来する生物種: Staphylococcus aureus (strain COL)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 302726.09

構造登録者

Hammerstad, M.,Hersleth, H.-P. (登録日: 2020-10-19, 公開日: 2020-12-30, 最終更新日: 2025-10-01)

主引用文献

Hammerstad, M.,Gudim, I.,Hersleth, H.P.
The Crystal Structures of Bacillithiol Disulfide Reductase Bdr (YpdA) Provide Structural and Functional Insight into a New Type of FAD-Containing NADPH-Dependent Oxidoreductase.
Biochemistry, 59:4793-4798, 2020

PubMed Abstract: Low G+C Gram-positive Firmicutes, such as the clinically important pathogens and , use the low-molecular weight thiol bacillithiol (BSH) as a defense mechanism to buffer the intracellular redox environment and counteract oxidative stress encountered by human neutrophils during infections. The protein YpdA has recently been shown to function as an essential NADPH-dependent reductase of oxidized bacillithiol disulfide (BSSB) resulting from stress responses and is crucial for maintaining the reduced pool of BSH and cellular redox balance. In this work, we present the first crystallographic structures of YpdAs, namely, those from and . Our analyses reveal a uniquely organized biological tetramer; however, the structure of the monomeric subunit is highly similar to those of other flavoprotein disulfide reductases. The absence of a redox active cysteine in the vicinity of the FAD isoalloxazine ring implies a new direct disulfide reduction mechanism, which is backed by the presence of a potentially gated channel, serving as a putative binding site for BSSB in the proximity of the FAD cofactor. We also report enzymatic activities for both YpdAs, which along with the structures presented in this work provide important structural and functional insight into a new class of FAD-containing NADPH-dependent oxidoreductases, related to the emerging fight against pathogenic bacteria.

PubMed: 33326741
DOI: 10.1021/acs.biochem.0c00745

実験手法

X-RAY DIFFRACTION (3.1 Å)