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 classic example of an allosteric protein and has been extensively studied biochemically, kinetically and structurally. As yet, however, a detailed model for the cooperative transition between the tensed (T) and relaxed (R) forms of the protein does not exist. In this work we have calculated the low frequency normal modes of the CTP-ligated T-state of ATCase with the aim of identifying some of the motions that could be important in initiating the transition. The calculated modes, of frequencies lower than 5 per cm, 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 displacements which change the quaternary structure of the protein (in particular the elongation of the protein and the relative rotation of the subunits) in such a way that the R-state structure is approached. The implication of these mode motions for the overall T-->R transition process is discussed.
Thomas
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Laboratoire de Dynamique Moléculaire, Institut de Biologie Structurale-Jean Pierre Ebel, Grenoble, France.
Field
M J
MJ
Mouawad
L
L
Perahia
D
D
D000495:Allosteric Site; D001221:Aspartate Carbamoyltransferase / Q000737:chemistry*; D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D003570:Cytidine Triphosphate / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D003570:Cytidine Triphosphate; D001221:Aspartate Carbamoyltransferase