Dynamics of protein ligand binding on multiple time scales

NADH binding to lactate dehydrogenase

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Although the importance of atomic motion to how proteins function has been conjectured for several decades, the characterization of protein dynamics on multiple time scales is scant. This is because of severe experimental and theoretical difficulties, particularly characterizing the nanosecond to millisecond time scales. Here, we apply advanced laser-induced temperature-jump relaxation spectroscopic techniques to examine the kinetics of NADH binding to lactate dehydrogenase over this time scale. The bimolecular rate process, at about 290 μs, is easily observed as are multiple faster events (with relaxation times of 200 ns, 3.5 μs, and 24 μs), revealing a rich dynamical nature of the binding step. The results show that there are multiple structures of bound enzyme - ligand complexes, some of which are likely to be far from the catalytically productive structure. The results have important implications for interpretations of the binding thermodynamics of ligands to LDH and, by extension, to other proteins. The observed processes likely play a role in the dynamics of the chemistry that is catalyzed by lactate dehydrogenase.

Original languageEnglish (US)
Pages (from-to)3767-3773
Number of pages7
JournalBiochemistry
Volume40
Issue number13
DOIs
StatePublished - Apr 3 2001

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L-Lactate Dehydrogenase
Protein Binding
NAD
Ligands
Proteins
Relaxation Therapy
Relaxation time
Thermodynamics
Lasers
Kinetics
Enzymes
Temperature

ASJC Scopus subject areas

  • Biochemistry

Cite this

Dynamics of protein ligand binding on multiple time scales : NADH binding to lactate dehydrogenase. / Deng, Hua; Zhadin, N.; Callender, Robert.

In: Biochemistry, Vol. 40, No. 13, 03.04.2001, p. 3767-3773.

Research output: Contribution to journalArticle

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