Catalytic Mechanism of Galactose Oxidase: A Theoretical Study

• DOI: 10.1021/ja994527r
• Publication Date: 2002-07-26T05:57:48Z
• Authors: Fahmi Himo; Leif A. Eriksson; Feliu Maseras; Per E. M. Siegbahn
• Keywords: Galactose oxidase; Ketyl; Hydrogen atom; Proton-Coupled Electron Transfer

Density functional methods, alone and together with molecular mechanics, are used to study the catalytic mechanism of galactose oxidase. This enzyme catalyzes conversion primary alcohols corresponding aldehydes, coupled reduction dioxygen hydrogen peroxide. It is shown that proposed for this energetically feasible. In particular barrier postulated rate-limiting atom transfer between substrate tyrosyl radical, located at equatorial Tyr272, very plausible. We propose radical site, prior initial proton step, axial tyrosine (Tyr495). The transferred (Tyr272) simultaneously transfer. is, furthermore, argued electron from ketyl intermediate Cu(II) cannot be exothermic, because would render oxygen steps rate-limiting. Finally, cysteine cross-link on active site have minor effects energetics reaction.