TY  - JOUR
AU  - Gruber, Karl
AU  - Csitkovits, Vanessa
AU  - Łyskowski, Andrzej
AU  - Kratky, Christoph
AU  - Kräutler, Bernhard
TI  - Structure‐Based Demystification of Radical Catalysis by a Coenzyme B<sub>12</sub> Dependent Enzyme—Crystallographic Study of Glutamate Mutase with Cofactor Homologues
JO  - Angewandte Chemie
VL  - 134
IS  - 35
SN  - 0932-2132
CY  - Weinheim
PB  - Wiley-VCH
M1  - PUBDB-2023-00367
SP  - e202208295
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1002/ange.202208295
UR  - https://bib-pubdb1.desy.de/record/491728
ER  -