4D7L

Methionine sulfoxide reductase A of Corynebacterium diphtheriae

4D7L の概要

• エントリーDOI: 10.2210/pdb4d7l/pdb
• 分子名称: PEPTIDE METHIONINE SULFOXIDE REDUCTASE MSRA, CACODYLATE ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: oxidoreductase, thiol disulfide exchange
• 由来する生物種: CORYNEBACTERIUM DIPHTHERIAE NCTC 13129
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 82083.92

構造登録者

Van Molle, I.,Tossounian, M.A.,Pedre, B.,Wahni, K.,Vertommen, D.,Messens, J. (登録日: 2014-11-25, 公開日: 2015-03-18, 最終更新日: 2024-10-23)

主引用文献

Tossounian, M.,Pedre, B.,Wahni, K.,Erdogan, H.,Vertommen, D.,Van Molle, I.,Messens, J.
Corynebacterium Diphtheriae Methionine Sulfoxide Reductase a Exploits a Unique Mycothiol Redox Relay Mechanism.
J.Biol.Chem., 290:11365-, 2015

PubMed Abstract: Methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. We have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is coupled to two independent redox relay pathways. Steady-state kinetics combined with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation reaction with an intramolecular disulfide bond cascade linked to the thioredoxin pathway. Within this cascade, the oxidative equivalents are transferred to the surface of the protein while releasing the reduced substrate. Alternatively, MsrA catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1 pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray crystallography, we visualize two essential intermediates of the thioredoxin relay mechanism and a cacodylate molecule mimicking the substrate interactions in the active site. The interplay of both redox pathways in redox signaling regulation forms the basis for further research into the oxidative stress response of this pathogen.

PubMed: 25752606
DOI: 10.1074/JBC.M114.632596

実験手法

X-RAY DIFFRACTION (1.895 Å)