Why are some Enzymes Dimers? Flexibility and Catalysis in Thermotoga Maritima Dihydrofolate Reductase.

ABSTRACT: Dihydrofolate Reductase from Thermotoga maritima (TmDFHFR) is a dimeric thermophilic enzyme that catalyzes the hydride transfer from the cofactor NADPH to dihydrofolate less efficiently than other DHFR enzymes, such as the mesophilic analogue Escherichia coli DHFR (EcDHFR). Using QM/MM potentials we show that the reduced catalytic efficiency of TmDHFR is most likely due to differences in the amino acid sequence that stabilize the M20 loop in an open conformation, which prevents the formation of some interactions in the transition state and increases the number of water molecules in the active site. However, dimerization provides two advantages to the thermophilic enzyme; it protects its structure against denaturation by reducing thermal fluctuations and it provides a less neg

SUBMITTER: Ruiz-Pernia JJ 

PROVIDER: S-EPMC6614790 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature