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Angew Chem Int Ed Engl. 2015 Jun 8;54(24):7158-61. doi: 10.1002/anie.201501930. Epub 2015 Apr 27.

Unprecedented Mechanism Employed by the Salmonella enterica EutT ATP:Co(I)rrinoid Adenosyltransferase Precludes Adenosylation of Incomplete Co(II)rrinoids.

Author information

1
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706 (USA).
2
Present address: Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon (Republic of Korea).
3
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706 (USA).
4
Present address: Department of Developmental Biology, Stanford University, Stanford, CA 94305 (USA).
5
Department of Microbiology, University of Georgia-Athens, Athens, GA 30602 (USA).
6
Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706 (USA). brunold@chem.wisc.edu.

Abstract

Three distinct families of ATP:corrinoid adenosyltransferases (ACATs) exist that are capable of converting vitamin B12 derivatives into coenzyme B12 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.

KEYWORDS:

adenosylcobalamin; adenosyltransferases; enzyme catalysis; reaction mechanisms; reduction

PMID:
25914129
PMCID:
PMC4504680
DOI:
10.1002/anie.201501930
[Indexed for MEDLINE]
Free PMC Article

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