Tryptophan tryptophylquinone biosynthesis: A radical approach to posttranslational modification
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- 作者：Victor L. Davidson ; Aimin Liu
- 关键词：MADH ; methylamine dehydrogenase ; TTQ ; tryptophan tryptophylquinone ; preMADH ; the biosynthetic precursor protein of MADH with incompletely synthesized TTQ ; bis-Fe(IV) MauG ; redox state of MauG with one heme as Fe(IV) ; = ; O and the other as Fe(IV)
- 刊名：Biochimica et Biophysica Acta - Proteins and Proteomics
- 出版年：2012
- 出版时间：November, 2012
- 年：2012
- 卷：1824
- 期：11
- 页码：1299-1305
- 全文大小：774 K
文摘
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.