Sequential model

This model for allosteric regulation of enzymes suggests that the subunits of multimeric proteins have two conformational states.

[5] Developed by Koshland, Némethy and Filmer in 1966, the KNF model describes cooperativity as a sequential process, where ligand binding alters the conformation, and thus the affinity, of proximal subunits of the protein, resulting in several different conformations that have varying affinities for a given ligand.

[5] A slight change in the conformation of an enzyme improves its binding affinity to the transition state of the ligand, thus catalyzing a reaction.

[2] This term is used merely to describe the structural nature of the sequential model, as the authors provide no other proposed descriptions or types of cooperativity.

The MWC model only allows for positive cooperativity, where a single conformational switch from the T to R states results in an increase in affinity for the ligand at unligated binding sites.

Negative cooperativity is observed in a number of biologically significant molecules, including tyrosyl-tRNA synthetase and glyceraldehyde-3-phosphate dehydrogenase.

[11] Thus, depending on physiological conditions, a combination of the MWC and KNF models appears to most comprehensively describe hemoglobin's binding characteristics.