Original scientific paper

https://doi.org/10.5562/cca3047

Xanthine Dehydrogenase Active Site: Chiral Switching and Substrate Coordination

Predrag-Peter Ilich ; Department of Biological Sciences, St. John’s University, New York City, NY 11439, USA

Abstract

Analysis of electronic, structural and mechanistic parameters of the enzyme-substrate reaction of xanthine oxidase, a member of the xanthine dehydrogenase class of mono-molybdopterin oxidoreductive enzymes, shows that the molybdenum center in the enzyme active site acts as a reversible chiral switch. The metal center cycles from the (S)-absolute configuration, SPY-5-42-A, in the fully oxidized state, Mo(VI), to the (R)-absolute configuration, SPY-5-43-C, for the fully reduced metal center, Mo(IV). This process is complemented by induction of chirality at the substrate carbon center (pro-SC → SC) and is involved in the control of coordination and, likely, protonation of imino-centers of conjugated heterocyclic substrates in the enzyme active site.

This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords

xanthine dehydrogenase; molybdopterin cofactor; oxidoreductive catalysis; first-principles electronic structure calculation; Mo-center chirality switching; enzyme-substrate coordination control

Hrčak ID:

179538

URI

https://hrcak.srce.hr/179538

Publication date:

19.12.2016.

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