Preservation of protein dynamics in dihydrofolate reductase evolution.

ABSTRACT: The hydride transfer reaction catalyzed by dihydrofolate reductase (DHFR) is a model for examining how protein dynamics contribute to enzymatic function. The relationship between functional motions and enzyme evolution has attracted significant attention. Recent studies on N23PP Escherichia coli DHFR (ecDHFR) mutant, designed to resemble parts of the human enzyme, indicated a reduced single turnover rate. NMR relaxation dispersion experiments with that enzyme showed rigidification of millisecond Met-20 loop motions (Bhabha, G., Lee, J., Ekiert, D. C., Gam, J., Wilson, I. A., Dyson, H. J., Benkovic, S. J., and Wright, P. E. (2011) Science 332, 234-238). A more recent study of this mutant, however, indicated that fast motions along the reaction coordinate are actually more dispersed than for

SUBMITTER: Francis K 

PROVIDER: S-EPMC3861645 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature