ANALYSIS OF THE LOW-FREQUENCY NORMAL-MODES OF THE T-STATE OF ASPARTATE-TRANSCARBAMYLASE

Aspartate transcarbamylase (ATCase) is an important control enzyme in the pyrimidine biosynthetic pathway in Escherichia coli. It is a class ic example of an allosteric protein and has been extensively studied b iochemically, kinetically and structurally As yet, however, a detailed model for the cooperative transition between the tensed (T) and relax ed (R) forms of the protein does not exist. In this work we have calcu lated the low frequency normal modes of the CTP-ligated T-state of ATC ase with the aim of identifying some of the motions that could be impo rtant in initiating the transition. The calculated modes, of frequenci es lower than 5 cm(-1), produce root-mean-square coordinate deviations for the atoms which are a substantial fraction of those derived from the crystallographic B-factors. Some of the modes result in displaceme nts which change the quaternary structure of the protein (in particula r the elongation of the protein and the relative rotation of the subun its) in such a way that the R-state structure is approached. The impli cation of these mode motions for the overall T-->R transition process is discussed. (C) 1996 Academic Press Limited