A hotspot of inactivation: The A22S and V108M polymorphisms individually destabilize the active site structure of catechol O-methyltransferase.

ABSTRACT: Human catechol O-methyltransferase (COMT) contains three common polymorphisms (A22S, A52T, and V108M), two of which (A22S and V108M) render the protein susceptible to deactivation by temperature or oxidation. We have performed multiple molecular dynamics simulations of the wild-type, A22S, A52T, and V108M COMT proteins to explore the structural consequences of these mutations. In total, we have amassed more than 1.4 micros of simulation time, representing the largest set of simulations detailing the effects of polymorphisms on a protein system to date. The A52T mutation had no significant effect on COMT structure in accord with experiment, thereby serving as a good negative control for the simulation set. Residues 22 (alpha2) and 108 (alpha5) interact with each other throughout the simulat

SUBMITTER: Rutherford K 

PROVIDER: S-EPMC2906713 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature