Uncovering novel biochemistry in the mechanism of tryptophan tryptophylquinone cofactor biosynthesis

Carrie M. Wilmot, Victor L. Davidson

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations

Abstract

Catalytic quinone cofactors derived from post-translational modification of amino acid residues within the enzyme polypeptide have roles in a variety of biological processes ranging from metabolism in bacteria to inflammation and connective tissue maturation in humans. In recent years, studies of the biosynthesis of one of these cofactors, tryptophan tryptophylquinone (TTQ), have provided examples of novel chemistry that is required for the generation of these protein-derived cofactors. A novel c-type diheme enzyme, MauG, catalyzes a six-electron oxidation that completes TTQ biosynthesis in a 119-kDa protein substrate. The post-translational modification reactions proceed via an unprecedented Fe(V) equivalent catalytic intermediate comprising two hemes; one an Fe(IV){double bond, long}O and the other a six-coordinate Fe(IV) with axial ligands provided by amino acid residues. This high-valent diheme species is an alternative to Compound I, an Fe(IV){double bond, long}O heme with a porphyrin or amino acid cation radical, which is typically the reactive intermediate of heme-dependent oxygenases and peroxidases.

Original languageEnglish (US)
Pages (from-to)469-474
Number of pages6
JournalCurrent opinion in chemical biology
Volume13
Issue number4
DOIs
StatePublished - Oct 2009

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grants GM-66569 (CMW) and GM-41574 (VLD).

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

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