A quantitative model of cooperative effects in aspartate transcarbamylase and related hybrid molecules.

Abstract

AbstractThe hypothesis is made that cooperative (homotropic) effects in aspartate transcarbamylase (ATCase) and closely related hybrid molecules can be treated on the same basis, by expressing the effects in terms of cooperative interactions between catalytic sites. Then, provided the hybrid CnnnCsss[R] exhibits cooperativity experimentally, it is deduced that at least two parameters are required for a consistent description of cooperative effects in ATCase.On this basis, a quantitative model is proposed that has cooperative interactions of two types: (1) a cooperative interaction of strength U between a pair of native catalytic sites situated in different catalytic trimers, and joined by a regulatory dimer; (2) an indirect cooperative interaction Ū, between any pair of native catalytic sites in the same catalytic trimer, which is transmitted via two regulatory dimers. The model is consistent with the observation that the isolated catalytic trimer does not exhibit cooperativity, and that cooperative effects require the integrity of the regulatory dimers.In this model, the hybrid molecule CnnnCsss[R] becomes simply a one‐dimensional Ising model for three sites with pair interactions Ū, and the hybrid CnssCnss[R] becomes an Ising model for two sites with interaction U/3. The model of native ATCase is essentially two Ising systems (the catalytic subunits), each with three sites having intrasubunit pair interactions Ū, coupled together with three intersubunit pair interactions U.The parameters Ū and U can be determined by comparing the exact solutions for the saturation curves of the two Ising models with the curves obtained from cooperativity measurements on the corresponding hybrid molecules. The theory can be readily tested, when accurate experimental data become available, by substituting the values of Ū and U determined from the hybrids into the model of native ATCase, or into models of other hybrids.