Multiple intermediates, diverse conformations, and cooperative conformational changes underlie the catalytic hydride transfer reaction of dihydrofolate reductase.

ABSTRACT: It has become increasingly clear that protein motions play an essential role in enzyme catalysis. However, exactly how these motions are related to an enzyme's chemical step is still intensely debated. This chapter examines the possible role of protein motions that display a hierarchy of timescales in enzyme catalysis. The linkage between protein motions and catalysis is investigated in the context of a model enzyme, E. coli dihydrofolate reductase (DHFR), that catalyzes the hydride transfer reaction in the conversion of dihydrofolate to tetrahydrofolate. The results of extensive computer simulations probing the protein motions that are manifest during different steps along the turnover cycle of DHFR are summarized. Evidence is presented that the protein motions modulate the catalytic effi

SUBMITTER: Arora K 

PROVIDER: S-EPMC4394636 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature