%0 Journal Article
%A Gruber, Karl
%A Csitkovits, Vanessa
%A Łyskowski, Andrzej
%A Kratky, Christoph
%A Kräutler, Bernhard
%T Structure‐Based Demystification of Radical Catalysis by a Coenzyme B<sub>12</sub> Dependent Enzyme—Crystallographic Study of Glutamate Mutase with Cofactor Homologues
%J Angewandte Chemie
%V 134
%N 35
%@ 0932-2132
%C Weinheim
%I Wiley-VCH
%M PUBDB-2023-00367
%P e202208295
%D 2022
%X Catalysis by radical enzymes dependent on coenzyme B<sub>12</sub> (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<sup>12</sup>-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.
%F PUB:(DE-HGF)16
%9 Journal Article
%R 10.1002/ange.202208295
%U https://bib-pubdb1.desy.de/record/491728