Catalytic contributions from remote regions of enzyme structure

Jeeyeon Lee, Nina Goodey

Research output: Contribution to journalReview articleResearchpeer-review

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7595-7624
Number of pages30
JournalChemical Reviews
Volume111
Issue number12
DOIs
StatePublished - 14 Dec 2011

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Enzymes
Potential energy
Hydrides
Escherichia coli
Catalysis
Free energy
Molecular dynamics
Hydrogen
Membrane Proteins
Proteins
Nuclear magnetic resonance
Atoms
Kinetics
Computer simulation
Direction compound

Cite this

Lee, Jeeyeon ; Goodey, Nina. / Catalytic contributions from remote regions of enzyme structure. In: Chemical Reviews. 2011 ; Vol. 111, No. 12. pp. 7595-7624.
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Catalytic contributions from remote regions of enzyme structure. / Lee, Jeeyeon; Goodey, Nina.

In: Chemical Reviews, Vol. 111, No. 12, 14.12.2011, p. 7595-7624.

Research output: Contribution to journalReview articleResearchpeer-review

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