Skip to main content
Journal cover image

Conformational selection or induced fit: a flux description of reaction mechanism.

Publication ,  Journal Article
Hammes, GG; Chang, Y-C; Oas, TG
Published in: Proc Natl Acad Sci U S A
August 18, 2009

The mechanism of ligand binding coupled to conformational changes in macromolecules has recently attracted considerable interest. The 2 limiting cases are the "induced fit" mechanism (binding first) or "conformational selection" (conformational change first). Described here are the criteria by which the sequence of events can be determined quantitatively. The relative importance of the 2 pathways is determined not by comparing rate constants (a common misconception) but instead by comparing the flux through each pathway. The simple rules for calculating flux in multistep mechanisms are described and then applied to 2 examples from the literature, neither of which has previously been analyzed using the concept of flux. The first example is the mechanism of conformational change in the binding of NADPH to dihydrofolate reductase. The second example is the mechanism of flavodoxin folding coupled to binding of its cofactor, flavin mononucleotide. In both cases, the mechanism switches from being dominated by the conformational selection pathway at low ligand concentration to induced fit at high ligand concentration. Over a wide range of conditions, a significant fraction of the flux occurs through both pathways. Such a mixed mechanism likely will be discovered for many cases of coupled conformational change and ligand binding when kinetic data are analyzed by using a flux-based approach.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 18, 2009

Volume

106

Issue

33

Start / End Page

13737 / 13741

Location

United States

Related Subject Headings

  • Tetrahydrofolate Dehydrogenase
  • Protein Folding
  • Protein Conformation
  • NADP
  • Molecular Conformation
  • Models, Theoretical
  • Models, Chemical
  • Magnetic Resonance Spectroscopy
  • Ligands
  • Kinetics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hammes, G. G., Chang, Y.-C., & Oas, T. G. (2009). Conformational selection or induced fit: a flux description of reaction mechanism. Proc Natl Acad Sci U S A, 106(33), 13737–13741. https://doi.org/10.1073/pnas.0907195106
Hammes, Gordon G., Yu-Chu Chang, and Terrence G. Oas. “Conformational selection or induced fit: a flux description of reaction mechanism.Proc Natl Acad Sci U S A 106, no. 33 (August 18, 2009): 13737–41. https://doi.org/10.1073/pnas.0907195106.
Hammes GG, Chang Y-C, Oas TG. Conformational selection or induced fit: a flux description of reaction mechanism. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13737–41.
Hammes, Gordon G., et al. “Conformational selection or induced fit: a flux description of reaction mechanism.Proc Natl Acad Sci U S A, vol. 106, no. 33, Aug. 2009, pp. 13737–41. Pubmed, doi:10.1073/pnas.0907195106.
Hammes GG, Chang Y-C, Oas TG. Conformational selection or induced fit: a flux description of reaction mechanism. Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13737–13741.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 18, 2009

Volume

106

Issue

33

Start / End Page

13737 / 13741

Location

United States

Related Subject Headings

  • Tetrahydrofolate Dehydrogenase
  • Protein Folding
  • Protein Conformation
  • NADP
  • Molecular Conformation
  • Models, Theoretical
  • Models, Chemical
  • Magnetic Resonance Spectroscopy
  • Ligands
  • Kinetics