Work

Network of coupled promoting motions in enzyme catalysis

Year: 2002

Type: article

Abstract: 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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.052005999

Authors: Pratul K. Agarwal, Salomon R. Billeter, P. T. Ravi Rajagopalan, Stephen J. Benkovic, Sharon Hammes-Schiffer

Institution: Pennsylvania State University

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Alfred P. Sloan Foundation, National Institutes of Health, National Institute of General Medical Sciences