Functionally important conformations of the Met20 loop in dihydrofolate reductase are populated by rapid thermal fluctuations.

ABSTRACT: Conformational changes in enzymes are well recognized to play an important role in the organization of the reactive groups for efficient catalysis. This study reveals atomic and energetic details of the conformational change process that precedes the catalytic reaction of the enzyme dihydrofolate reductase. The computed free energy profile provides insights into the ligand binding mechanism and a quantitative estimate of barrier heights separating different conformational states along the pathway. Studies show that the ternary complex comprised of NADPH cofactor and substrate dihydrofolate undergoes transitions between a closed state and an occluded state via an intermediate "open" conformation. During these transitions the largest conformational change occurs in the Met20 loop of DHFR and

SUBMITTER: Arora K 

PROVIDER: S-EPMC2889193 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature