Structural highlights
Function
[TSTD1_HUMAN] Thiosulfate:glutathione sulfurtransferase (TST) required to produce glutathione persulfide (GSS(-)), a central intermediate in hydrogen sulfide metabolism (PubMed:24981631). Provides the link between the first step in mammalian H(2)S metabolism performed by the sulfide:quinone oxidoreductase (SQOR) which catalyzes the conversion of H(2)S to thiosulfate, and the sulfur dioxygenase (SDO) which uses GSS(-) as substrate (PubMed:24981631). The thermodynamic coupling of the irreversible SDO and reversible TST reactions provides a model for the physiologically relevant reaction with thiosulfate as the sulfane donor (PubMed:24981631).[1]
Publication Abstract from PubMed
Rhodanese domains are structural modules present in the sulfurtransferase superfamily. These domains can exist as single units, in tandem repeats or fused to domains with other activities. Despite their prevalence across species, the specific physiological roles of most sulfurtransferases are not known. Mammalian rhodanese and mercaptopyruvate sulfurtransferase are perhaps the best-studied members of this protein superfamily and are involved in hydrogen sulfide metabolism. The relatively unstudied human thiosulfate sulfurtransferase like domain-containing 1 (TSTD1) protein, a single-domain cytoplasmic sulfurtransferase, was also postulated to play a role in the sulfide oxidation pathway using thiosulfate to form glutathione persulfide, for subsequent processing in the mitochondrial matrix. Prior kinetic analysis of TSTD1 was performed at pH 9.2, raising questions about relevance and the proposed model for TSTD1 function. In this study, we report a 1.04 A resolution crystal structure of human TSTD1, which displays an exposed active site that is distinct from that of rhodanese and mercaptopyruvate sulfurtransferase. Kinetic studies with a combination of sulfur donors and acceptors reveal that TSTD1 exhibits a low KM for thioredoxin as a sulfane sulfur acceptor and that it utilizes thiosulfate inefficiently as a sulfur donor. The active site exposure and its interaction with thioredoxin, suggest that TSTD1 might play a role in sulfide-based signaling. The apical localization of TSTD1 in human colonic crypts, which interfaces with sulfide-releasing microbes, and the overexpression of TSTD1 in colon cancer, provides potentially intriguing clues as to its role in sulfide metabolism.
Thiosulfate Sulfurtransferase like Domain Containing 1 Protein Interacts with Thioredoxin.,Libiad M, Motl N, Akey DL, Sakamoto N, Fearon ER, Smith JL, Banerjee R J Biol Chem. 2018 Jan 18. pii: RA117.000826. doi: 10.1074/jbc.RA117.000826. PMID:29348167[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Melideo SL, Jackson MR, Jorns MS. Biosynthesis of a central intermediate in hydrogen sulfide metabolism by a novel human sulfurtransferase and its yeast ortholog. Biochemistry. 2014 Jul 22;53(28):4739-53. doi: 10.1021/bi500650h. Epub 2014 Jul, 10. PMID:24981631 doi:http://dx.doi.org/10.1021/bi500650h
- ↑ Libiad M, Motl N, Akey DL, Sakamoto N, Fearon ER, Smith JL, Banerjee R. Thiosulfate Sulfurtransferase like Domain Containing 1 Protein Interacts with Thioredoxin. J Biol Chem. 2018 Jan 18. pii: RA117.000826. doi: 10.1074/jbc.RA117.000826. PMID:29348167 doi:http://dx.doi.org/10.1074/jbc.RA117.000826
