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 N alpha-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 language | English |
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Pages (from-to) | 48219-48227 |
Number of pages | 9 |
Journal | Journal of Biological Chemistry |
Volume | 278 |
Issue number | 48 |
DOIs | |
Publication status | Published - 28 Nov 2003 |
Externally published | Yes |
Keywords
- Amino Acid Sequence
- Animals
- Binding Sites
- Catalysis
- Catalytic Domain
- Cattle
- Crystallography, X-Ray
- Cysteine
- Dose-Response Relationship, Drug
- Hydrolysis
- Immunosuppressive Agents
- Leishmania major
- Models, Chemical
- Models, Molecular
- Molecular Sequence Data
- Protein Conformation
- Protein Folding
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Serine Endopeptidases
- Sulfurtransferases
- Tacrolimus
- Thiosulfate Sulfurtransferase