Open AccessDifferent Dynamical Effects in Mesophilic and Hyperthermophilic Dihydrofolate Reductases
Author(s) -
Louis Y. P. Luk,
E. Joel Loveridge,
Rudolf K. Allemann
Publication year - 2014
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/ja502673h
Subject(s) - chemistry , dihydrofolate reductase , thermotoga maritima , hyperthermophile , kinetic isotope effect , enzyme catalysis , catalysis , enzyme , reaction coordinate , hydride , mesophile , escherichia coli , protein dynamics , reactivity (psychology) , stereochemistry , biochemistry , computational chemistry , protein structure , deuterium , organic chemistry , bacteria , hydrogen , alternative medicine , pathology , archaea , genetics , biology , quantum mechanics , medicine , physics , gene
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.
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