The crystal structure of Leishmania major 3-mercaptopyruvate sulfurtransferase: A three-domain architecture with a serine protease-like triad at the active site

Magnus S. Alphey, Roderick Williams, Jeremy Mottram, Graham Coombs, William N. Hunter

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Leishmania major 3-mercaptopyruvate sulfurtransferase is a crescent-shaped molecule comprising three domains. The N-terminal and central domains are similar to the thiosulfate sulfurtransferase rhodanese and create the active site containing a persulfurated catalytic cysteine (Cys-253) and an inhibitory sulfite coordinated by Arg-74 and Arg-185. A serine protease-like triad, comprising Asp-61, His-75, and Ser-255, is near Cys-253 and represents a conserved feature that distinguishes 3-mercaptopyruvate sulfurtransferases from thiosulfate sulfurtransferases. During catalysis, Ser-255 may polarize the carbonyl group of 3-mercaptopyruvate to assist thiophilic attack, whereas Arg-74 and Arg-185 bind the carboxylate group. The enzyme hydrolyzes benzoyl-Arg-p-nitroanilide, an activity that is sensitive to the presence of the serine protease inhibitor Nα-p-tosyl-l-lysine chloromethyl ketone, which also lowers 3-mercaptopyruvate sulfurtransferase activity, presumably by interference with the contribution of Ser-255. The L. major 3-mercaptopyruvate sulfurtransferase is unusual with an 80-amino acid C-terminal domain, bearing remarkable structural similarity to the FK506-binding protein class of peptidylprolyl cis/trans-isomerase. This domain may be involved in mediating protein folding and sulfurtransferase-protein interactions.
Original languageEnglish
Pages (from-to)48219-48227
Number of pages9
JournalJournal of Biological Chemistry
Volume278
DOIs
Publication statusPublished - 1 Sep 2003

Keywords

  • Leishmania major
  • protein
  • sulfurtransferase-protein
  • crystal structure

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