Enzyme Catalysis that Paves the Way for S-Sulfhydration via Sulfur Atom Transfer
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- 作者：Gou-Tao Huang ; Jen-Shiang K. Yu
- 刊名：Journal of Physical Chemistry B
- 出版年：2016
- 出版时间：May 26, 2016
- 年：2016
- 卷：120
- 期：20
- 页码：4608-4615
- 全文大小：520K
- 年卷期：0
- ISSN：1520-5207
文摘
S-sulfhydration is generally anticipated to proceed through the transfer of the SH group (Nu–SH···–S–R → Nu–···HS–S–R). The other route involves the sulfur atom (S0) transfer between two sulfhydryl anions (Nu–S–···–S–R → Nu–···–S–S–R) and is considered electrostatically unfavorable. Mercaptopyruvate sulfurtransferase (MST, PDB code: 4JGT) catalyzes sulfur transfer from mercaptopyruvate to sulfur acceptors, and the first step of the reaction is the formation of cysteine (Cys248) persulfide via S-sulfhydration. Mechanistic studies on S-sulfhydration in MST using QM/MM methods show that the sulfur atom transfer initialized by the deprotonation of the Ser250/His74/Asp63 triad is kinetically preferred to the SH-promoted sulfur transfer. The calculated barrier of approximately 16 kcal mol–1 for the S0 transfer agrees well with experimental results. The electrostatic repulsion during the S0 transfer can be sophisticatedly reduced by the aid of the Cys248-Gly249-Ser250-Gly251-Val252-Thr253 (CGSGVT) loop. Electrostatic potentials and frontier orbitals are also analyzed for the persulfide anion surrounded by the loop. The sulfur atom transfer which is seldom regarded possible is therefore facilitated with the assistance of the triad and the loop in the enzyme.