 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 ( 15n , 13c , 2h ) . 
 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 . 
Supplementary Material