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How the Co-C bond is cleaved in coenzyme B-12 enzymes: A theoretical study

Jensen, Kasper LU and Ryde, Ulf LU (2005) In Journal of the American Chemical Society 127(25). p.9117-9128
Abstract
The homolytic cleavage of the organometallic Co-C bond in vitamin B-12-dependent enzymes is accelerated by a factor of similar to 10(12) in the protein compared to that of the isolated cofactor in aqueous solution. To understand this much debated effect, we have studied the Co-C bond cleavage in the enzyme glutamate mutase with combined quantum and molecular mechanics methods. We show that the calculated bond dissociation energy (BDE) of the Co-C bond in adenosyl cobalamin is reduced by 135 kJ/mol in the enzyme. This catalytic effect can be divided into four terms. First, the adenosine radical is kept within 4.2 angstrom of the Cc ion in the enzyme, which decreases the BDE by 20 kJ/mol. Second, the surrounding enzyme stabilizes the... (More)
The homolytic cleavage of the organometallic Co-C bond in vitamin B-12-dependent enzymes is accelerated by a factor of similar to 10(12) in the protein compared to that of the isolated cofactor in aqueous solution. To understand this much debated effect, we have studied the Co-C bond cleavage in the enzyme glutamate mutase with combined quantum and molecular mechanics methods. We show that the calculated bond dissociation energy (BDE) of the Co-C bond in adenosyl cobalamin is reduced by 135 kJ/mol in the enzyme. This catalytic effect can be divided into four terms. First, the adenosine radical is kept within 4.2 angstrom of the Cc ion in the enzyme, which decreases the BDE by 20 kJ/mol. Second, the surrounding enzyme stabilizes the dissociated state by 42 kJ/mol using electrostatic and van der Waals interactions. Third, the protein itself is stabilized by 11 kJ/mol in the dissociated state. Finally, the coenzyme is geometrically distorted by the protein, and this distortion is 61 kJ/mol larger in the Co-III state. This deformation of the coenzyme is caused mainly by steric interactions, and it is especially the ribose moiety and the Co-C5'-C4' angle that are distorted. Without the polar ribose group, the catalytic effect is much smaller, e.g. only 42 kJ/mol for methyl cobalamin. The deformation of the coenzyme is caused mainly by the substrate, a side chain of the coenzyme itself, and a few residues around the adenosine part of the coenzyme. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Chemical Society
volume
127
issue
25
pages
9117 - 9128
publisher
The American Chemical Society
external identifiers
  • wos:000230010600053
  • pmid:15969590
  • scopus:21344463602
ISSN
1520-5126
DOI
10.1021/ja050744i
language
English
LU publication?
yes
id
1a14d6cc-0df2-4755-b593-cddaf6605857 (old id 152743)
date added to LUP
2007-07-17 10:57:48
date last changed
2017-09-03 04:32:46
@article{1a14d6cc-0df2-4755-b593-cddaf6605857,
  abstract     = {The homolytic cleavage of the organometallic Co-C bond in vitamin B-12-dependent enzymes is accelerated by a factor of similar to 10(12) in the protein compared to that of the isolated cofactor in aqueous solution. To understand this much debated effect, we have studied the Co-C bond cleavage in the enzyme glutamate mutase with combined quantum and molecular mechanics methods. We show that the calculated bond dissociation energy (BDE) of the Co-C bond in adenosyl cobalamin is reduced by 135 kJ/mol in the enzyme. This catalytic effect can be divided into four terms. First, the adenosine radical is kept within 4.2 angstrom of the Cc ion in the enzyme, which decreases the BDE by 20 kJ/mol. Second, the surrounding enzyme stabilizes the dissociated state by 42 kJ/mol using electrostatic and van der Waals interactions. Third, the protein itself is stabilized by 11 kJ/mol in the dissociated state. Finally, the coenzyme is geometrically distorted by the protein, and this distortion is 61 kJ/mol larger in the Co-III state. This deformation of the coenzyme is caused mainly by steric interactions, and it is especially the ribose moiety and the Co-C5'-C4' angle that are distorted. Without the polar ribose group, the catalytic effect is much smaller, e.g. only 42 kJ/mol for methyl cobalamin. The deformation of the coenzyme is caused mainly by the substrate, a side chain of the coenzyme itself, and a few residues around the adenosine part of the coenzyme.},
  author       = {Jensen, Kasper and Ryde, Ulf},
  issn         = {1520-5126},
  language     = {eng},
  number       = {25},
  pages        = {9117--9128},
  publisher    = {The American Chemical Society},
  series       = {Journal of the American Chemical Society},
  title        = {How the Co-C bond is cleaved in coenzyme B-12 enzymes: A theoretical study},
  url          = {http://dx.doi.org/10.1021/ja050744i},
  volume       = {127},
  year         = {2005},
}