Interaction of protein with a self-associating ligand. Deviation from a hyperbolic binding curve and the appearance of apparent co-operativity in the Scatchard plot

J Theor Biol. 1988 Jan 7;130(1):49-66. doi: 10.1016/s0022-5193(88)80163-2.

Abstract

We derived a general formula to analyze a binding system in which a ligand self-associates, in terms of experimentally determinable quantities, i.e. r, the average number of bound ligands per protein molecule, and Lft, the total free ligand concentration, which are expressed as a ligand monomer unit. The limiting behaviors of the Scatchard plot (r/Lft vs r plot), that is, the intercepts on the r-axis and the r/Lft-axis, and the limiting slopes, are generally given. Three models that may be encountered are considered in detail. Numerical examples are also presented to illustrate how the self-association of a ligand affects the binding curves. The ligand self-association alone can cause deviation of the profile of the binding curve (r vs Lft plot) from a hyperbola, resulting in a nonlinear Scatchard plot. Therefore, analysis of the binding data without consideration of ligand self-association may lead to erroneous conclusions as to the numbers and classes of binding sites, co-operativity among the sites and binding parameter values.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Kinetics
  • Ligands / metabolism*
  • Macromolecular Substances
  • Mathematics
  • Models, Biological
  • Proteins / metabolism*
  • Thermodynamics

Substances

  • Ligands
  • Macromolecular Substances
  • Proteins