1. Functional and structural characterization of a flavoprotein monooxygenase essential for biogenesis of tryptophylquinone cofactor.
- Author
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Oozeki, Toshinori, Nakai, Tadashi, Kozakai, Kazuki, Okamoto, Kazuki, Kuroda, Shun'ichi, Kobayashi, Kazuo, Tanizawa, Katsuyuki, and Okajima, Toshihide
- Subjects
POST-translational modification ,FLAVIN adenine dinucleotide ,BACTERIAL enzymes ,CHEMICAL reactions ,SIGNAL recognition particle receptor ,FLAVOPROTEINS ,AMINE oxidase - Abstract
Bioconversion of peptidyl amino acids into enzyme cofactors is an important post-translational modification. Here, we report a flavoprotein, essential for biosynthesis of a protein-derived quinone cofactor, cysteine tryptophylquinone, contained in a widely distributed bacterial enzyme, quinohemoprotein amine dehydrogenase. The purified flavoprotein catalyzes the single-turnover dihydroxylation of the tryptophylquinone-precursor, tryptophan, in the protein substrate containing triple intra-peptidyl crosslinks that are pre-formed by a radical S-adenosylmethionine enzyme within the ternary complex of these proteins. Crystal structure of the peptidyl tryptophan dihydroxylase reveals a large pocket that may dock the protein substrate with the bound flavin adenine dinucleotide situated close to the precursor tryptophan. Based on the enzyme-protein substrate docking model, we propose a chemical reaction mechanism of peptidyl tryptophan dihydroxylation catalyzed by the flavoprotein monooxygenase. The diversity of the tryptophylquinone-generating systems suggests convergent evolution of the peptidyl tryptophan-derived cofactors in different proteins. An important type of post-translational protein modification is the conversion of peptidyl amino acid into enzyme cofactor. Here, the authors report functional and structural characterization of a flavoprotein monooxygenase essential for biosynthesis of cysteine tryptophylquinone (CTQ) cofactor. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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