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 (<sup>15</sup>N, <sup>13</sup>C, <sup>2</sup>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