3-mercaptopyruvate sulfurtransferase

 

Sulfurtransferases (EC 2.8.1.1–5) catalyze the transfer of sulfane sulfur from a donor molecule to a thiophilic acceptor. These enzymes are widely distributed in plants, animals, and bacteria and have been implicated in a wide range of biological processes. The archetypal sulfurtransferase is rhodanese, a thiosulfate: cyanide sulfurtransferase (TST) able to catalyse the transfer of the thiosulfate sulfur to cyanide in vitro. The related 3-mercaptopyruvate sulfurtransferase (3-mercaptopyruvate:cyanide sulfurtransferase (MST)), first discovered in rat liver, catalyses reactions similar to those catalysed by rhodanese, but uses 3-mercaptopyruvate in preference to thiosulfate as the donor in the two-step reaction.

 

Reference Protein and Structure

Sequence
Q7K9G0 UniProt (2.8.1.2) IPR001763 (Sequence Homologues) (PDB Homologues)
Biological species
Leishmania major (Leishmania) Uniprot
PDB
1okg - 3-mercaptopyruvate sulfurtransferase from Leishmania major (2.1 Å) PDBe PDBsum 1okg
Catalytic CATH Domains
3.40.250.10 CATHdb (see all for 1okg)
Cofactors
Zinc(2+) (1)
Click To Show Structure

Enzyme Reaction (EC:2.8.1.2)

3-mercaptopyruvate
CHEBI:57678ChEBI
+
hydrogen cyanide
CHEBI:18407ChEBI
→
hydron
CHEBI:15378ChEBI
+
pyruvate
CHEBI:15361ChEBI
+
thiocyanate
CHEBI:18022ChEBI
Alternative enzyme names: Beta-mercaptopyruvate sulfurtransferase, TUM1 (gene name), MPST (gene name), 3-mercaptopyruvate:cyanide sulfurtransferase,

Enzyme Mechanism

Introduction

The mechanism of the catalysis has been mostly presumed to be a double displacement via the ternary complex of 3MST, 3MP and thiophiles. Here, the nucleophilic cysteine residue abstracts the sulfur from the donor, forming the persulfide and the pyruvate product. This activated persulfide that transfers the sulfate to an acceptor.

Catalytic Residues Roles

UniProt PDB* (1okg)
Cys253 Css253A Acts as a catalytic nucleophile, is modified to a persulfide. proton shuttle (general acid/base)
Asp61, His75 Asp61A, His75A Part of the Ser-His-Asp triad that activates the nucleophilic cysteine residue. electrostatic stabiliser
Ser255 Ser255A Ser-255 could contribute to the binding of 3-mercaptopyruvate by interaction with the carbonyl group. Such an interaction could polarize the carbonyl group and serve to enhance nucleophilic attack by the Cys-253 thiolate, allowing the enzyme to then attain the persulfide form by turnover of the appropriate sulfur donor. Is part of a Ser-His-Asp triad. enhance reactivity, electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. Alphey MS et al. (2003), J Biol Chem, 278, 48219-48227. The Crystal Structure ofLeishmania major3-Mercaptopyruvate Sulfurtransferase. DOI:10.1074/jbc.m307187200. PMID:12952945.
  2. Hanaoka K et al. (2017), Sci Rep, 7, 40227-. Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide. DOI:10.1038/srep40227. PMID:28079151.

Step 1.

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Catalytic Residues Roles

Residue Roles
Ser255A electrostatic stabiliser, enhance reactivity
Css253A proton shuttle (general acid/base)
Asp61A electrostatic stabiliser
His75A electrostatic stabiliser

Chemical Components

Step 1.

Contributors

Alex Gutteridge, Craig Porter, Gemma L. Holliday