4JGT

Structure and kinetic analysis of H2S production by human Mercaptopyruvate Sulfurtransferase

4JGT の概要

• エントリーDOI: 10.2210/pdb4jgt/pdb
• 分子名称: 3-mercaptopyruvate sulfurtransferase, PYRUVIC ACID, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: rhodanese, transferase, 3-mercaptopyruvate sulfurtransferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): P25325
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 101620.65

構造登録者

Koutmos, M.,Yamada, K.,Yadav, P.K.,Chiku, T.,Banerjee, R. (登録日: 2013-03-03, 公開日: 2013-05-29, 最終更新日: 2024-11-27)

主引用文献

Yadav, P.K.,Yamada, K.,Chiku, T.,Koutmos, M.,Banerjee, R.
Structure and Kinetic Analysis of H2S Production by Human Mercaptopyruvate Sulfurtransferase.
J.Biol.Chem., 288:20002-20013, 2013

PubMed Abstract: Mercaptopyruvate sulfurtransferase (MST) is a source of endogenous H2S, a gaseous signaling molecule implicated in a wide range of physiological processes. The contribution of MST versus the other two H2S generators, cystathionine β-synthase and γ-cystathionase, has been difficult to evaluate because many studies on MST have been conducted at high pH and have used varied reaction conditions. In this study, we have expressed, purified, and crystallized human MST in the presence of the substrate 3-mercaptopyruvate (3-MP). The kinetics of H2S production by MST from 3-MP was studied at pH 7.4 in the presence of various physiological persulfide acceptors: cysteine, dihydrolipoic acid, glutathione, homocysteine, and thioredoxin, and in the presence of cyanide. The crystal structure of MST reveals a mixture of the product complex containing pyruvate and an active site cysteine persulfide (Cys(248)-SSH) and a nonproductive intermediate in which 3-MP is covalently linked via a disulfide bond to an active site cysteine. The crystal structure analysis allows us to propose a detailed mechanism for MST in which an Asp-His-Ser catalytic triad is positioned to activate the nucleophilic cysteine residue and participate in general acid-base chemistry, whereas our kinetic analysis indicates that thioredoxin is likely to be the major physiological persulfide acceptor for MST.

PubMed: 23698001
DOI: 10.1074/jbc.M113.466177

実験手法

X-RAY DIFFRACTION (2.161 Å)