Premium
Unprecedented Mechanism Employed by the Salmonella enterica EutT ATP:Co I rrinoid Adenosyltransferase Precludes Adenosylation of Incomplete Co II rrinoids
Author(s) -
Park Kiyoung,
Mera Paola E.,
Moore Theodore C.,
EscalanteSemerena Jorge C.,
Brunold Thomas C.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201501930
Subject(s) - corrinoid , cofactor , chemistry , adenosylcobalamin , enzyme , stereochemistry , corrin , ligand (biochemistry) , substrate (aquarium) , divalent , biochemistry , vitamin b12 , biology , receptor , organic chemistry , methylation , ecology , methyltransferase , gene
Three distinct families of ATP:corrinoid adenosyltransferases (ACATs) exist that are capable of converting vitamin B 12 derivatives into coenzyme B 12 by catalyzing the thermodynamically challenging reduction of Co II rrinoids to form “supernucleophilic” Co I intermediates. While the structures and mechanisms of two of the ACAT families have been studied extensively, little is known about the EutT enzymes beyond the fact that they exhibit a unique requirement for a divalent metal cofactor for enzymatic activity. In this study we have obtained compelling evidence that EutT converts cob(II)alamin into an effectively four‐coordinate Co II species so as to facilitate Co II →Co I reduction. Intriguingly, EutT fails to promote axial ligand dissociation from the substrate analogue cob(II)inamide, a natural precursor of cob(II)alamin. This unique substrate specificity of EutT has important physiological implications.