Hydride Transfer by Dihydrofolate Reductase
نویسندگان
چکیده
منابع مشابه
Hydride transfer during catalysis by dihydrofolate reductase from Thermotoga maritima.
DHFR (dihydrofolate reductase) catalyses the metabolically important reduction of 7,8-dihydrofolate by NADPH. DHFR from the hyperthermophilic bacterium Thermotoga maritima (TmDHFR), which shares similarity with DHFR from Escherichia coli, has previously been characterized structurally. Its tertiary structure is similar to that of DHFR from E. coli but it is the only DHFR characterized so far th...
متن کاملExtension and Limits of the Network of Coupled Motions Correlated to Hydride Transfer in Dihydrofolate Reductase
Enzyme catalysis has been studied extensively, but the role of enzyme dynamics in the catalyzed chemical conversion is still an enigma. The enzyme dihydrofolate reductase (DHFR) is often used as a model system to assess a network of coupled motions across the protein that may affect the catalyzed chemical transformation. Molecular dynamics simulations, quantum mechanical/molecular mechanical st...
متن کاملSmall temperature dependence of the kinetic isotope effect for the hydride transfer reaction catalyzed by Escherichia coli dihydrofolate reductase.
The H/D primary kinetic isotope effect (KIE) for the hydride transfer reaction catalyzed by Escherichia coli dihydrofolate reductase (ecDHFR) is calculated as a function of temperature employing ensemble-averaged variational transition-state theory with multidimensional tunneling. The calculated KIEs display only a small temperature dependence over the temperature range of 5 to 45 degrees C. We...
متن کاملThe role of enzyme dynamics and tunnelling in catalysing hydride transfer: studies of distal mutants of dihydrofolate reductase.
Residues M42 and G121 of Escherichia coli dihydrofolate reductase (ecDHFR) are on opposite sides of the catalytic centre (15 and 19 A away from it, respectively). Theoretical studies have suggested that these distal residues might be part of a dynamics network coupled to the reaction catalysed at the active site. The ecDHFR mutant G121V has been extensively studied and appeared to have a signif...
متن کاملThe role of enzyme dynamics and tunnelling in catalysing hydride transfer: studies of distal mutants of dihydrofolate reductase Published online
Residues M42 and G121 of Escherichia coli dihydrofolate reductase (ecDHFR) are on opposite sides of the catalytic centre (15 and 19 Å away from it, respectively). Theoretical studies have suggested that these distal residues might be part of a dynamics network coupled to the reaction catalysed at the active site. The ecDHFR mutant G121V has been extensively studied and appeared to have a signif...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 1989
ISSN: 0021-9258
DOI: 10.1016/s0021-9258(18)60544-7