Tryptophan tryptophylquinone biosynthesis: A radical approach to posttranslational modification

    Authors

    V. L. Davidson;A. M. Liu

    Comments

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    Abbreviated Journal Title

    BBA-Proteins Proteomics

    Keywords

    Cytochrome; Electron transfer; Ferryl intermediate; Heme; MauG; Methylamine dehydrogenase; ELECTRON-TRANSFER COMPLEX; CYTOCHROME-C PEROXIDASE; METHYLAMINE; DEHYDROGENASE; PARACOCCUS-DENITRIFICANS; CRYSTAL-STRUCTURE; MAUG; AMICYANIN; PROTEIN; COFACTOR; MUTAGENESIS; Biochemistry & Molecular Biology; Biophysics

    Abstract

    Protein-derived cofactors are formed by irreversible covalent posttranslational modification of amino acid residues. An example is tryptophan tryptophylquinone (TTQ) found in the enzyme methylamine dehydrogenase (MADH). TTQ biosynthesis requires the cross-linking of the indole rings of two Trp residues and the insertion of two oxygen atoms onto adjacent carbons of one of the indole rings. The diheme enzyme MauG catalyzes the completion of TTQ within a precursor protein of MADH. The preMADH substrate contains a single hydroxyl group on one of the tryptophans and no crosslink. MauG catalyzes a six-electron oxidation that completes TTQ assembly and generates fully active MADH. These oxidation reactions proceed via a high valent bis-Fe(IV) state in which one heme is present as Fe(IV)=O and the other is Fe(IV) with both axial heme ligands provided by amino acid side chains. The crystal structure of MauG in complex with preMADH revealed that catalysis does not involve direct contact between the hemes of MauG and the protein substrate. Rather it is accomplished through long-range electron transfer, which presumably generates radical intermediates. Kinetic, spectrophotometric, and site-directed mutagenesis studies are beginning to elucidate how the MauG protein controls the reactivity of the hemes and mediates the long range electron/radical transfer required for catalysis. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology. (C) 2012 Elsevier B.V. All rights reserved.

    Journal Title

    Biochimica Et Biophysica Acta-Proteins and Proteomics

    Volume

    1824

    Issue/Number

    11

    Publication Date

    1-1-2012

    Document Type

    Review

    Language

    English

    First Page

    1299

    Last Page

    1305

    WOS Identifier

    WOS:000309298900014

    ISSN

    1570-9639

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