Structure-Based Demystification of Radical Catalysis by a Coenzyme B 12 Dependent Enzyme-Crystallographic Study of Glutamate Mutase with Cofactor Homologues.

Autor: Gruber K; Institute of Molecular Biosciences University of Graz Humboldtstraße 50 8010 Graz Austria.; BioTechMed-Graz 8010 Graz Austria.; Field of Excellence 'BioHealth' University of Graz 8010 Graz Austria., Csitkovits V; Institute of Molecular Biosciences University of Graz Humboldtstraße 50 8010 Graz Austria., Łyskowski A; Institute of Molecular Biosciences University of Graz Humboldtstraße 50 8010 Graz Austria.; Present address: Department of Biotechnology and Bioinformatics Rzeszów University of Technology al. Powstańców Warszawy 12 35-959 Rzeszów Poland., Kratky C; Institute of Molecular Biosciences University of Graz Humboldtstraße 50 8010 Graz Austria., Kräutler B; Institute of Organic Chemistry University of Innsbruck Innrain 80/82 6020 Innsbruck Austria.; Center of Molecular Biosciences (CMBI) University of Innsbruck 6020 Innsbruck Austria.
Jazyk: angličtina
Zdroj: Angewandte Chemie (Weinheim an der Bergstrasse, Germany) [Angew Chem Weinheim Bergstr Ger] 2022 Aug 26; Vol. 134 (35), pp. e202208295. Date of Electronic Publication: 2022 Jul 21.
DOI: 10.1002/ange.202208295
Abstrakt: Catalysis by radical enzymes dependent on coenzyme B 12 (AdoCbl) relies on the reactive primary 5'-deoxy-5'adenosyl radical, which originates from reversible Co-C bond homolysis of AdoCbl. This bond homolysis is accelerated roughly 10 12 -fold upon binding the enzyme substrate. The structural basis for this activation is still strikingly enigmatic. As revealed here, a displaced firm adenosine binding cavity in substrate-loaded glutamate mutase (GM) causes a structural misfit for intact AdoCbl that is relieved by the homolytic Co-C bond cleavage. Strategically interacting adjacent adenosine- and substrate-binding protein cavities provide a tight caged radical reaction space, controlling the entire radical path. The GM active site is perfectly structured for promoting radical catalysis, including "negative catalysis", a paradigm for AdoCbl-dependent mutases.
Competing Interests: The authors declare no conflict of interest.
(© 2022 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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