Toggle Main Menu Toggle Search

Open Access padlockePrints

Understanding the mechanism of B12-dependent methylmalonyl-CoA mutase: partial proton transfer in action

Lookup NU author(s): Professor Bernard Golding

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Ab initio molecular orbital theory is used to investigate several possible mechanisms involving free radical intermediates for the coenzyme- B12-dependent rearrangement catalyzed by methylmalonyl-CoA mutase. Our calculations suggest that an intermolecular pathway in which transient fragmentation of the substrate-derived radical is followed by recombination of the fragments ('fragmentation-recombination') is unlikely, but not out of the question. An alternative intramolecular pathway ('addition-elimination') is found to be energetically more favorable. Protonation of the species involved in this latter pathway is found to further reduce the barrier for rearrangement. Examination of the middle ground between the protonated and unprotonated intramolecular mechanisms reveals a continuous spectrum of behavior and demonstrates the potential importance of partial proton transfer. Support for this proposal is obtained from the X-ray crystal structure of the protein. The stereochemistry of the rearrangement has also been examined and leads to a new proposal consistent with experiment.


Publication metadata

Author(s): Smith DM, Golding BT, Radom L

Publication type: Article

Publication status: Published

Journal: Journal of the American Chemical Society

Year: 1999

Volume: 121

Issue: 40

Pages: 9388-9399

Print publication date: 13/10/1999

ISSN (print): 0002-7863

ISSN (electronic):

URL: http://dx.doi.org/10.1021/ja991649a

DOI: 10.1021/ja991649a


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share