6BEV

Human Single Domain Sulfurtranferase TSTD1

6BEV の概要

• エントリーDOI: 10.2210/pdb6bev/pdb
• 分子名称: Thiosulfate sulfurtransferase/rhodanese-like domain-containing protein 1 (2 entities in total)
• 機能のキーワード: sulfurtransferase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29431.17

構造登録者

Motl, N.,Akey, D.L.,Smith, J.L.,Banerjee, R. (登録日: 2017-10-25, 公開日: 2018-01-24, 最終更新日: 2024-03-13)

主引用文献

Libiad, M.,Motl, N.,Akey, D.L.,Sakamoto, N.,Fearon, E.R.,Smith, J.L.,Banerjee, R.
Thiosulfate sulfurtransferase-like domain-containing 1 protein interacts with thioredoxin.
J. Biol. Chem., 293:2675-2686, 2018

PubMed 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 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.

PubMed: 29348167
DOI: 10.1074/jbc.RA117.000826

実験手法

X-RAY DIFFRACTION (1.043 Å)