Linked Life Data

21476560

Source:http://linkedlifedata.com/resource/pubmed/id/21476560

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-4-28
pubmed:abstractText
QM/MD simulations are performed to study mutational effects on the glycosylation step of the oligosaccharide hydrolysis catalyzed by Trichoderma reesei cellobiohydrolase I. The potential of mean force along the reaction pathway is determined by the umbrella sampling method. A detailed mechanism is developed to illustrate the decrease in activity of the mutants. Our calculations demonstrate that (1) the E212Q mutation increases the overall activation barrier by ~4.0 kcal/mol, while the D214N mutation causes ~0.4 kcal/mol increase of the barrier, and (2) there is only one transition state identified in the wild type (WT) and D214N mutant, while two transition states exist in the E212Q mutant for the glycosylation process. The results explain the experimental observation that the E212Q mutant loses most of its hydrolysis capability, while the D214N mutant only reduces it slightly compared to the WT. Further analysis suggests that the proton transfer from Glu(217) to O(4) and the glycosidic bond cleavage between subsites +1 and -1 are concerted, facilitating the subsequent nucleophilic attack of Glu(212) on C(1)' in subsite -1. Our QM/MD study illustrates the importance of the prearrangement of the active site and provides atomic details of the enzymatic catalytic mechanism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1520-5207
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4982-9
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Mutational effects on the catalytic mechanism of cellobiohydrolase I from Trichoderma reesei.
pubmed:affiliation
Key Lab of Biofuels, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't