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      Thiosulfate sulfurtransferase-like domain–containing 1 protein interacts with thioredoxin

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          Abstract

          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 Å 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 K m 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 provide potentially intriguing clues as to its role in sulfide metabolism.

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          Author and article information

          Journal
          J Biol Chem
          J. Biol. Chem
          jbc
          jbc
          JBC
          The Journal of Biological Chemistry
          American Society for Biochemistry and Molecular Biology (11200 Rockville Pike, Suite 302, Rockville, MD 20852-3110, U.S.A. )
          0021-9258
          1083-351X
          23 February 2018
          18 January 2018
          : 293
          : 8
          : 2675-2686
          Affiliations
          From the []Department of Biological Chemistry,
          the [§ ]Life Sciences Institute, and
          the []Departments of Internal Medicine, Human Genetics, and Pathology, University of Michigan Medical Center, Ann Arbor, Michigan 48109 and
          the []Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
          Author notes
          [2 ] To whom correspondence should be addressed. Tel.: 734-615-5238; E-mail: rbanerje@ 123456umich.edu .
          [1]

          Both authors contributed equally to this work.

          Edited by F. Peter Guengerich

          Article
          PMC5827441 PMC5827441 5827441 RA117.000826
          10.1074/jbc.RA117.000826
          5827441
          29348167
          89bc8c48-371f-48ba-924d-576d6fbf152c
          © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
          History
          : 6 November 2017
          : 16 January 2018
          Funding
          Funded by: HHS National Institutes of Health (NIH) , open-funder-registry 10.13039/100000002;
          Award ID: GM112455
          Award ID: T32GM008353
          Categories
          Enzymology

          enzyme kinetics,sulfur,hydrogen sulfide,sulfur transferase,post-translational modification (PTM),crystal structure

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