Changes in protein architecture and subpicosecond protein dynamics impact the reaction catalyzed by lactate dehydrogenase

Jean E. Masterson, Steven D Schwartz

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

We have previously established the importance of a promoting vibration, a subpicosecond protein motion that propagates through a specific axis of residues, in the reaction coordinate of lactate dehydrogenase (LDH). To test the effect that perturbation of this motion would have on the enzymatic reaction, we employ transition path sampling to obtain transition path ensembles for four independent LDH enzymatic systems: the wild type enzyme, a version of the enzyme expressing heavy isotopic substitution, and two enzymes with mutations in the promoting vibration axis. We show that even slight changes in the promoting vibration of LDH result in dramatic changes in enzymatic chemistry. In the "heavy" version of the enzyme, we find that the dampening of the subpicosecond dynamics from heavy isotopic substitution leads to a drastic increase in the time of barrier crossing. Furthermore, we see that mutation of the promoting vibration axis causes a decrease in the variability of transition paths available to the enzymatic reaction. The combined results reveal the importance of the protein architecture of LDH in enzymatic catalysis by establishing how the promoting vibration is finely tuned to facilitate chemistry.

Original languageEnglish (US)
Pages (from-to)7107-7113
Number of pages7
JournalJournal of Physical Chemistry A
Volume117
Issue number32
DOIs
StatePublished - Aug 15 2013

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lactates
dehydrogenases
L-Lactate Dehydrogenase
enzymes
proteins
vibration
Enzymes
mutations
Proteins
Substitution reactions
substitutes
chemistry
Catalysis
catalysis
Sampling
sampling
perturbation
causes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry

Cite this

Changes in protein architecture and subpicosecond protein dynamics impact the reaction catalyzed by lactate dehydrogenase. / Masterson, Jean E.; Schwartz, Steven D.

In: Journal of Physical Chemistry A, Vol. 117, No. 32, 15.08.2013, p. 7107-7113.

Research output: Contribution to journalArticle

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