MPST (22q12.3) Merkaptopyruvaatti sulfurtransferaasi, MST, TST2, TUM1

 Siirtää rikkijonin (S)  syanidille (CN)  merkaptopalorypälehapolta.

Official Symbol MPST

Official Full Name mercaptopyruvate sulfurtransferase

Gene type protein coding

Also known as MST; TST2; TUM1

Summary  This protein encoded by this gene catalyzes the transfer of a sulfur ion from 3-mercaptopyruvate to cyanide or other thiol compounds. It may be involved in cysteine degradation and cyanide detoxification. There is confusion in literature between this protein (mercaptopyruvate sulfurtransferase, MPST), which appears to be cytoplasmic, and thiosulfate sulfurtransferase (rhodanese, TST, GeneID:7263), which is a mitochondrial protein.

 Deficiency in MPST activity has been implicated in a rare inheritable disorder known as mercaptolactate-cysteine disulfiduria (MCDU). Alternatively spliced transcript variants encoding same or different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Expression

Ubiquitous expression in duodenum (RPKM 33.5), liver (RPKM 30.3) and 25 other tissues See more

Orthologsmouse all

 

1. Characterization and interaction studies of two isoforms of the dual localized 3-mercaptopyruvate sulfurtransferase TUM1 from humans. Fräsdorf B, et al. J Biol Chem, 2014 Dec 12. PMID 25336638, Free PMC Article
2. Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. Yadav PK, et al. J Biol Chem, 2013 Jul 5. PMID 23698001, Free PMC Article 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 (CBS)  and γ-cystathionase (CTH) , 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.
3. Evidence for a functional genetic polymorphism of the human mercaptopyruvate sulfurtransferase (MPST), a cyanide detoxification enzyme. Billaut-Laden I, et al. Toxicol Lett, 2006 Aug 20. PMID 16545926Mercaptopyruvate sulfurtransferase (MPST) plays a central role in both cysteine degradation and cyanide detoxification. Moreover, deficiency in MPST activity has been suggested to be responsible for a rare inheritable disorder known as mercaptolactate-cysteine disulfiduria (MCDU). To date, no mutation of the human MPST gene has been reported. We developed a screening strategy to search for mutations in the MPST gene of 50 unrelated French individuals. Two intronic polymorphisms (IVS1-110C>G and IVS2+39C>T) and a nonsense mutation (Tyr(85)Stop) were identified and their functional consequences were assessed in vivo by measurement of erythrocyte MPST activity and/or in vitro using heterologous expression or transient transfection assay. The nonsense mutation likely leads to the synthesis of a severely truncated protein without enzymatic activity, as supported by our in vitro data. This work constitutes the first report of the existence of a functional genetic polymorphism affecting MPST and should be of great help to investigate certain disorders such as MCDU.
4. Cloning and sequence analysis of the human liver rhodanese: comparison with the bovine and chicken enzymes. Pallini R, et al. Biochem Biophys Res Commun, 1991 Oct 31. PMID 1953758
5. The non-canonical Hippo/Mst pathway in lymphocyte development and functions. Du X, et al. Acta Biochim Biophys Sin (Shanghai), 2015 Jan. PMID 25487919