Remote mutations and active site dynamics correlate with catalytic properties of purine nucleoside phosphorylase.

ABSTRACT: It has been found that with mutation of two surface residues (Lys(22) --> Glu and His(104) --> Arg) in human purine nucleoside phosphorylase (hPNP), there is an enhancement of catalytic activity in the chemical step. This is true although the mutations are quite remote from the active site, and there are no significant changes in crystallographic structure between the wild-type and mutant active sites. We propose that dynamic coupling from the remote residues to the catalytic site may play a role in catalysis, and it is this alteration in dynamics that causes an increase in the chemical step rate. Computational results indicate that the mutant exhibits stronger coupling between promotion of vibrations and the reaction coordinate than that found in native hPNP. Power spectra comparing nativ

SUBMITTER: Saen-Oon S 

PROVIDER: S-EPMC2367194 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature