JBC, Vol. 250, Issue 2, 668-674, Jan, 1975
Subunit interactions in aspartate transcarbamylase. A model for the allosteric mechanism
W. W. Chan
The conformational changes in aspartate transcarbamylase upon binding of
substrates or regulatory ligands and the effects of alterations in the
subunit structure on the allosteric interactions are reviewed. The
available information including recent results from studies of the c3r6
complex (c denotes the catalytic polypeptide and r, the regulatory
polypeptide) is considered in terms of the existing models for the
discrepancies between experimental observations and the present models
could be resolved by postulating an important role for r:r interactions in
the allosteric mechanism. A new model is presented in which an obligatory
conformational change upon binding of substrates results in an alteration
in the relative orientation of c versus r. As a consequence of symmetry
conservation, the r:r domain is shifted to a position of higher potential
energy. By favoring one or the other alternative r:r domains, CTP and ATP
can respectively enhance and reduce the sigmoidal character of substrate
saturation. The model is shown to be consistent with all of the important
known properties of the enzyme. Because the heterotropic effects of CTP or
ATP are postulated to operate via a mechanism separate from that for the
homotropic effects of the substrates, this model accounts satisfactorily
for the observation by Kerbiriou and Herve (Kerbiriou, D., and Herve, G.
(1973) J. Mol. Biol. 78, 687-702) that homotropic effects can be abolished
whereas heterotropic effects are retained in the altered enzyme from
Escherichia coli grown in the presence of 2-thiouracil.
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