Structural origins for the loss of catalytic activities of bifunctional human LTA4H revealed through molecular dynamics simulations.

ABSTRACT: Human leukotriene A4 hydrolase (hLTA4H), which is the final and rate-limiting enzyme of arachidonic acid pathway, converts the unstable epoxide LTA4 to a proinflammatory lipid mediator LTB4 through its hydrolase function. The LTA4H is a bi-functional enzyme that also exhibits aminopeptidase activity with a preference over arginyl tripeptides. Various mutations including E271Q, R563A, and K565A have completely or partially abolished both the functions of this enzyme. The crystal structures with these mutations have not shown any structural changes to address the loss of functions. Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in cat

SUBMITTER: Thangapandian S 

PROVIDER: S-EPMC3405069 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature