Format

Send to

Choose Destination
J Am Chem Soc. 2005 Jun 1;127(21):7660-1.

Spectroscopic evidence for the formation of a four-coordinate Co2+ cobalamin species upon binding to the human ATP:cobalamin adenosyltransferase.

Author information

1
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

Abstract

The human adenosyltransferase hATR converts exogenous cobalamin into coenzyme B12 by transferring the adenosyl group from cosubstrate ATP to a transiently formed Co1+cobalamin (Co1+Cbl) species. A particularly puzzling aspect of hATR function is that the midpoint potential for Co2+Cbl --> Co1+Cbl reduction is below that of readily available biological reductants. Our magnetic circular dichroism and electron paramagnetic resonance spectroscopic studies reported here reveal that, in the absence of ATP, the interaction between Co2+Cbl and hATR promotes partial conversion of the cofactor to its "base-off" form in which a water molecule occupies the lower axial position. This interaction becomes much stronger in the presence of ATP, leading to the formation of an unprecedented Co2+Cbl species with spectroscopic signatures consistent with an essentially four-coordinate, square-planar Co2+ center. This unusual Co2+Cbl coordination is expected to raise the Co2+/1+ reduction potential well into the physiological range.

PMID:
15913339
DOI:
10.1021/ja050546r
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center