Linked Life Data

19715325

Source:http://linkedlifedata.com/resource/pubmed/id/19715325

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2009-11-12
pubmed:abstractText
The newly discovered SpvC effector protein from Salmonella typhimurium interferes with the host immune response by dephosphorylating mitogen-activated protein kinases (MAPKs) with a beta-elimination mechanism. To understand this unique phosphothreonine lyase catalysis, the dynamics of the enzyme-substrate complex of the SpvC effector is investigated with a 3.2 ns molecular dynamics simulation, which reveals that the phosphorylated peptide substrate is tightly held in the active site by a hydrogen bond network and the lysine general base is positioned for the abstraction of the alpha hydrogen. The catalysis is further modeled with density functional theory (DFT) in a truncated active-site model at the B3LYP/6-31+G(d,p) level of theory. The DFT calculations indicate the reaction proceeds via a single transition state, featuring a concerted proton abstraction from the alpha-carbon by Lys136 and beta-elimination of the phosphate leaving group. Key kinetic isotopic effects are predicted based on the truncated active-site model.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1520-5207
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15327-33
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Active-site dynamics of SpvC virulence factor from Salmonella typhimurium and density functional theory study of phosphothreonine lyase catalysis.
pubmed:affiliation
Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico, 87131, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural