Linked Life Data

20575011

Source:http://linkedlifedata.com/resource/pubmed/id/20575011

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-6-29
pubmed:abstractText
The catalytic mechanism of Mus musculus adenosine deaminase (ADA) has been studied by quantum mechanics and two-layered ONIOM calculations. Our calculations show that the previously proposed mechanism, involving His238 as the general base to activate the Zn-bound water, has a high activation barrier of about 28 kcal/mol at the proposed rate-determining nucleophilic addition step, and the corresponding calculated kinetic isotope effects are significantly different from the recent experimental observations. We propose a revised mechanism based on calculations, in which Glu217 serves as the general base to abstract the proton of the Zn-bound water, and the protonated Glu217 then activates the substrate for the subsequent nucleophilic addition. The rate-determining step is the proton transfer from Zn-OH to 6-NH(2) of the tetrahedral intermediate, in which His238 serves as a proton shuttle for the proton transfer. The calculated kinetic isotope effects agree well with the experimental data, and calculated activation energy is also consistent with the experimental reaction rate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1096-987X
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Wiley Periodicals, Inc.
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2238-47
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
A theoretical study on the catalytic mechanism of Mus musculus adenosine deaminase.
pubmed:affiliation
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't