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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Hammes, GG; Chang, Y-C; Oas, TG

Published Date

  • August 18, 2009

Published In

Volume / Issue

  • 106 / 33

Start / End Page

  • 13737 - 13741

PubMed ID

  • 19666553

Pubmed Central ID

  • PMC2728963

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.0907195106


  • eng

Conference Location

  • United States