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Electronic structure contributions to reactivity in xanthine oxidase family enzymes

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Abstract

We review the xanthine oxidase (XO) family of pyranopterin molybdenum enzymes with a specific emphasis on electronic structure contributions to reactivity. In addition to xanthine and aldehyde oxidoreductases, which catalyze the two-electron oxidation of aromatic heterocycles and aldehyde substrates, this mini-review highlights recent work on the closely related carbon monoxide dehydrogenase (CODH) that catalyzes the oxidation of CO using a unique Mo–Cu heterobimetallic active site. A primary focus of this mini-review relates to how spectroscopy and computational methods have been used to develop an understanding of critical relationships between geometric structure, electronic structure, and catalytic function.

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Abbreviations

AO:

Aldehyde oxidase

CODH:

CO dehydrogenase

DFT:

Density functional theory

ENDOR:

Electron–nuclear double resonance

EPR:

Electron paramagnetic resonance

EXAFS:

Extended X-ray absorption fine structure

FAD:

Flavin adenine dinucleotide

MCD:

Magnetic circular dichroism

QM/MM:

Quantum mechanics/molecular mechanics

ROS:

Reactive oxygen species

rR:

Resonance Raman

XDH/XO/XOR:

Xanthine dehydrogenase/oxidase/oxidoreductase

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Acknowledgments

M. L. K. would like to thank all of his graduate students and postdoctoral associates who have contributed to works described in this chapter. M. L. K. also acknowledges the National Institutes of Health (GM-057378) for continued support of the author’s work that is detailed in this review.

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Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, University of New Mexico, MSC03 2060, 300 Terrace St. NE, Albuquerque, NM, 87131, USA

    Benjamin W. Stein & Martin L. Kirk

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  1. Benjamin W. Stein
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Correspondence to Martin L. Kirk.

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Responsible Editors: José Moura and Paul Bernhardt.

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Stein, B.W., Kirk, M.L. Electronic structure contributions to reactivity in xanthine oxidase family enzymes. J Biol Inorg Chem 20, 183–194 (2015). https://doi.org/10.1007/s00775-014-1212-8

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