title: Understanding the mechanism of deacylation reaction catalyzed by the serine carboxyl peptidase kumamolisin-As: insights from QM/MM free energy simulations.
abstract: Quantum mechanical/molecular mechanical (QM/MM) molecular dynamics and free energy simulations are performed to study the process of the deacylation reaction catalyzed by kumamolisin-As, a serine-carboxyl peptidase, and to elucidate the catalytic mechanism. The results given here suggest that Asp-164 acts as a general acid/base catalyst not only for the acylation reaction but also for the deacylation reaction. It is shown that the electrostatic oxyanion hole interactions may be less effective in transition state stabilization for the kumamolisin-As catalyzed reaction compared to the general acid/base mechanism involving the proton transfer from or to Asp-164. The dynamic substrate-assisted catalysis (DSAC) involving His at the P1 site of the substrate is found to be less important for the deacylation reaction than for the acylation reaction in the kumamolisin-As catalyzed reaction. The proton transfer processes during the enzyme-catalyzed process are examined and their role in the catalysis is discussed.
authors: Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee 37996, USA.
authors: Qin
authors: Q
authors: Xu
authors: Liyan
authors: L
authors: Li
authors: Hong
authors: H
authors: Guo
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D003198:Computer Simulation; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D016282:Aspartic Acid Endopeptidases; C078894:kumamolysin