Title: Enzyme Catalysis that Paves the Way for S-Sulfhydration via Sulfur Atom Transfer
Authors: Huang, Gou-Tao
Yu, Jen-Shiang K.
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
Issue Date: 26-May-2016
Abstract: S-sulfhydration is generally anticipated to proceed through the transfer of the SH group (Nu-SH center dot center dot center dot S--R -> Nu(-)center dot center dot center dot HS-S-R). The other route involves the sulfur atom (5) transfer between two sulfhydryl anions (Nu-S-center dot center dot center dot S--R -> Nu(-)center dot center dot center dot 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 S-0 transfer agrees well with experimental results. The electrostatic repulsion during the S-0 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.
URI: http://dx.doi.org/10.1021/acs.jpcb.6b03387
ISSN: 1520-6106
DOI: 10.1021/acs.jpcb.6b03387
Volume: 120
Issue: 20
Begin Page: 4608
End Page: 4615
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