Institute of Molecular Biosciences, University of Graz, Humboldtstraße 50, 8010, Graz, Austria.
BioTechMed-Graz, 8010, Graz, Austria.
Angew Chem Int Ed Engl. 2022 Aug 26;61(35):e202208295. doi: 10.1002/anie.202208295. Epub 2022 Jul 21.
Catalysis by radical enzymes dependent on coenzyme B (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 -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.
依赖辅酶 B（AdoCbl）的自由基酶催化依赖于反应性的初始 5'-脱氧-5'腺苷自由基，该自由基源自 AdoCbl 的可逆 Co-C 键均裂。这种键均裂在与酶底物结合时会加速约 10 倍。这种激活的结构基础仍然非常神秘。如本文所揭示的，负载底物的谷氨酸变位酶（GM）中腺苷的位移固定结合腔导致完整的 AdoCbl 结构不匹配，这种不匹配通过均裂 Co-C 键的断裂得到缓解。策略性相互作用的相邻腺苷和底物结合蛋白腔提供了一个紧密的笼状自由基反应空间，控制整个自由基路径。GM 活性位点的结构非常适合促进自由基催化，包括“负催化”，这是 AdoCbl 依赖的变位酶的范例。
