Linked Life Data

12707799

Source:http://linkedlifedata.com/resource/pubmed/id/12707799

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-7-1
pubmed:abstractText
The mechanism and potential energy surface for the Baeyer-Villiger oxidation of acetone with hydrogen peroxide catalyzed by a Ser105-Ala mutant of Candida antarctica Lipase B has been determined using ab initio and density functional theories. Initial substrate binding has been studied using an automated docking procedure and molecular dynamics simulations. Substrates were found to bind to the active site of the mutant. The activation energy for the first step of the reaction, the nucleophilic attack of hydrogen peroxide on the carbonyl carbon of hydrogen peroxide, was calculated to be 4.4 kcal x mol(-1) at the B3LYP/6-31+G* level. The second step, involving the migration of the alkyl group, was found to be the rate-determining step with a computed activation energy of 19.9 kcal x mol(-1) relative the reactant complex. Both steps were found to be lowered considerably in the reaction catalyzed by the mutated lipase, compared to the uncatalyzed reaction. The first step was lowered by 36.0 kcal x mol(-1) and the second step by 19.5 kcal x mol(-1). The second step of the reaction, the rearrangement step, has a high barrier of 27.7 kcal x mol(-1) relative to the Criegee intermediate. This could lead to an accumulation of the intermediate. It is not clear whether this result is an artifact of the computational procedure, or an indication that further mutations of the active site are required. Figure Second TS (18TS) in the Baeyer-Villiger oxidation in a mutant of CALB. Distances in A
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0948-5023
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
164-71
pubmed:dateRevised
2006-12-12
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Rational design of a lipase to accommodate catalysis of Baeyer-Villiger oxidation with hydrogen peroxide.
pubmed:affiliation
Physical Chemistry, Royal Institute of Technology, 100 44, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't