The effect of active-site isoleucine to alanine mutation on the DHFR catalyzed hydride-transfer.

Comparison of the nature of hydride transfer in wild-type and active site mutant (I14A) of dihydrofolate reductase suggests that the size of this side chain at position 14 modulates H-tunneling.

[1]  Charles L. Brooks III,et al.  Functionally important conformations of the Met20 loop in dihydrofolate reductase are populated by rapid thermal fluctuations. , 2009, Journal of the American Chemical Society.

[2]  A. Warshel,et al.  Origin of the temperature dependence of isotope effects in enzymatic reactions: the case of dihydrofolate reductase. , 2007, The journal of physical chemistry. B.

[3]  N. Goodey,et al.  Coordinated effects of distal mutations on environmentally coupled tunneling in dihydrofolate reductase , 2006, Proceedings of the National Academy of Sciences.

[4]  A. Kohen,et al.  Analytical Procedures for the Preparation, Isolation, Analysis and Preservation of Reduced Nicotinamides , 2006 .

[5]  D. Boehr,et al.  The Dynamic Energy Landscape of Dihydrofolate Reductase Catalysis , 2006, Science.

[6]  N. Goodey,et al.  The role of enzyme dynamics and tunnelling in catalysing hydride transfer: studies of distal mutants of dihydrofolate reductase , 2006, Philosophical Transactions of the Royal Society B: Biological Sciences.

[7]  J. Klinman,et al.  Tunneling and dynamics in enzymatic hydride transfer. , 2006, Chemical reviews.

[8]  W. Huskey Isotope Effects in Chemistry and Biology Edited by Amnon Kohen (University of Iowa) and Hans-Heinrich Limbach (Freie Universität Berlin). CRC Press/Taylor and Francis Group: Boca Raton, FL. 2006. xiv + 1074 pp. $229.95. ISBN 0-9247-2449-6. , 2006 .

[9]  Sharon Hammes-Schiffer,et al.  Hydrogen tunneling and protein motion in enzyme reactions , 2006, Accounts of chemical research.

[10]  S. Benkovic,et al.  Effects of a distal mutation on active site chemistry. , 2006, Biochemistry.

[11]  Sharon Hammes-Schiffer,et al.  Impact of distal mutations on the network of coupled motions correlated to hydride transfer in dihydrofolate reductase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Benkovic,et al.  Tunneling and coupled motion in the Escherichia coli dihydrofolate reductase catalysis. , 2004, Journal of the American Chemical Society.

[13]  Peter E Wright,et al.  Effect of cofactor binding and loop conformation on side chain methyl dynamics in dihydrofolate reductase. , 2004, Biochemistry.

[14]  D. Truhlar,et al.  Reaction-path energetics and kinetics of the hydride transfer reaction catalyzed by dihydrofolate reductase. , 2003, Biochemistry.

[15]  Sharon Hammes-Schiffer,et al.  Nuclear Quantum Effects and Enzyme Dynamics in Dihydrofolate Reductase Catalysis , 2002 .

[16]  C. Brooks,et al.  Protein Dynamics in Enzymatic Catalysis: Exploration of Dihydrofolate Reductase , 2000 .

[17]  J. Ulstrup,et al.  Proton and hydrogen atom tunnelling in hydrolytic and redox enzyme catalysis , 1999 .

[18]  J. Klinman,et al.  Active site modifications in a double mutant of liver alcohol dehydrogenase: structural studies of two enzyme-ligand complexes. , 1998, Biochemistry.

[19]  J. Klinman,et al.  A link between protein structure and enzyme catalyzed hydrogen tunneling. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[20]  J. Kraut,et al.  Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence. , 1997, Biochemistry.

[21]  S. Benkovic,et al.  The function of amino acid residues contacting the nicotinamide ring of NADPH in dihydrofolate reductase from Escherichia coli. , 1991, Biochemistry.

[22]  S. Benkovic,et al.  Construction and evaluation of the kinetic scheme associated with dihydrofolate reductase from Escherichia coli. , 1987, Biochemistry.

[23]  W. Saunders,et al.  Reaction Rates of Isotopic Molecules , 1987 .

[24]  R. P. Bell,et al.  The tunnel effect in chemistry , 1959 .