TY - JOUR
T1 - Network of coupled promoting motions in enzyme catalysis
AU - Agarwal, Pratul K.
AU - Billeter, Salomon R.
AU - Rajagopalan, P. T.Ravi
AU - Benkovic, Stephen J.
AU - Hammes-Schiffer, Sharon
PY - 2002/3/5
Y1 - 2002/3/5
N2 - A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized. The present identification is based on genomic analysis for sequence conservation, kinetic measurements of multiple mutations, and mixed quantum/classical molecular dynamics simulations of hydride transfer. The motions in this network span time scales of femtoseconds to milliseconds and are found on the exterior of the enzyme as well as in the active site. This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site.
AB - A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized. The present identification is based on genomic analysis for sequence conservation, kinetic measurements of multiple mutations, and mixed quantum/classical molecular dynamics simulations of hydride transfer. The motions in this network span time scales of femtoseconds to milliseconds and are found on the exterior of the enzyme as well as in the active site. This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site.
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U2 - 10.1073/pnas.052005999
DO - 10.1073/pnas.052005999
M3 - Article
C2 - 11867722
AN - SCOPUS:0037022683
SN - 0027-8424
VL - 99
SP - 2794
EP - 2799
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -