Catalytic Contributions from Remote Regions of Enzyme Structure

Document Type

Article

Publication Date

12-14-2011

Abstract

Studies on the effects of distal mutations are presented that have refined perspective into the origins of enzymatic catalysis. A novel method was applied to egelin C where NMR-detected hydrogen exchange was used to measure pairwise and higher-order coupling long-range free energies that allowed for efficient analysis of a large number of couplings. In classical molecular dynamics simulations, the interaction between atoms is described by a classical force field which describes the potential energy of the protein. The complete kinetic scheme for E. coli DHFR has been determined and it is found that hydride-transfer step can also occur in the reverse direction from the occluded complex. Unlike most proteins, an extensive network of coupled residues has been characterized in DHFR. The network extends from the active site to the surface of the protein and the motions observed in the network residues span the time scales of femtoseconds to milliseconds.

DOI

10.1021/cr100042n

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