Active-site dynamics of SpvC virulence factor from Salmonella typhimurium and density functional theory study of phosphothreonine lyase catalysis.

ABSTRACT: 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

SUBMITTER: Smith GK 

PROVIDER: S-EPMC2783390 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature