Different dynamical effects in mesophilic and hyperthermophilic dihydrofolate reductases.
The role of protein dynamics in the reaction catalyzed by dihydrofolate reductase from the hyperthermophile Thermotoga maritima (TmDHFR) has been examined by enzyme isotope substitution ((15)N, (13)C, (2)H). In contrast to all other enzyme reactions investigated previously, including DHFR from Escherichia coli (EcDHFR), for which isotopic substitution led to decreased reactivity, the rate constant for the hydride transfer step is not affected by isotopic substitution of TmDHFR. TmDHFR therefore appears to lack the coupling of protein motions to the reaction coordinate that have been identified for EcDHFR catalysis. Clearly, dynamical coupling is not a universal phenomenon that affects the efficiency of enzyme catalysis.
School of Chemistry, Cardiff University , Main Building, Park Place, Cardiff CF10 3AT, United Kingdom.
Louis Y P
LY
Luk
E Joel
EJ
Loveridge
Rudolf K
RK
Allemann
D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D020124:Thermotoga maritima / Q000737:chemistry / Q000201:enzymology*
D013762:Tetrahydrofolate Dehydrogenase