Abstract

3-Mercaptopyruvate sulfurtransferase (MPST) catalyzes the desulfuration of 3-mercaptopyruvate to generate an enzyme-bound hydropersulfide. Subsequently, MPST transfers the persulfide's outer sulfur atom to proteins or small molecule acceptors. MPST activity is known to be involved in hydrogen sulfide generation, tRNA thiolation, protein urmylation and cyanide detoxification. Tissue-specific changes in MPST expression correlate with ageing and the development of metabolic disease. Deletion and overexpression experiments suggest that MPST contributes to oxidative stress resistance, mitochondrial respiratory function and the regulation of fatty acid metabolism. However, the role and regulation of MPST in the larger physiological context remain to be understood.

Highlights

  • Enzymology and structure of Mercaptopyruvate sulfurtransferase (MPST)In 1968, the analysis of urine from 2000 subjects led to the discovery of a previously unknown sulfur-containing metabolite, 3-mercaptolactate (3ML), in one of the subjects (Crawhall et al 1968)

  • MPST activity is known to be involved in hydrogen sulfide generation, tRNA thiolation, protein urmylation and cyanide detoxification

  • Unlike the MPST active site persulfide, the small molecule and Trx persulfides are not shielded against nucleophilic attack at the inner sulfur atom

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Summary

Enzymology and structure of MPST

In 1968, the analysis of urine from 2000 subjects (in the context of cystinuria screening) led to the discovery of a previously unknown sulfur-containing metabolite, 3-mercaptolactate (3ML), in one of the subjects (Crawhall et al 1968). Following binding into the active site pocket, 3MP is desulfurated, to generate a persulfidated active site cysteine and pyruvate as products. Pyruvate is released from the active site, allowing acceptor molecules to enter. MPST facilitates transfer of the outer sulfur atom of the enzyme-bound persulfide to the acceptor molecule (a process known as ‘transpersulfidation’), after which the sulfurated acceptor is released. The release of pyruvate is thought to be the ratelimiting step of the MPST catalytic cycle, but sulfur transfer may be rate-limiting, depending on the acceptor molecule (Lec et al 2018). MPST can be inhibited by its product pyruvate, but only at very high concentrations

This work is licensed under the Creative Commons Attribution
SH N
Sulfur acceptors for MPST
Thiolcontaining proteins
MPST SSH pyruvate
Subcellular localization of MPST
Posttranslational modifications of MPST
Tissue distribution of mammalian MPST
Phylogenetic distribution and gene organization of MPST
Regulation of MPST expression and its connection to physiology
Exon Intron
Pharmacological inhibitors of MPST
Phenotypes of MPST deficiency
Future perspectives
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