Allosteric control of quaternary states in E. coli aspartate transcarbamylase.
Changes in the molecular dimensions of ATCase in the unligated T-state are an increase of 0.4 A in the separation of catalytic trimers when ATP binds. When the R-state is produced by binding of phosphonoacetamide and malonate, addition of CTP or CTP + UTP decreases the separation of catalytic trimers by 0.5 A. In the unliganded Glu239----Gln mutant, in which the T-state is destabilized so that the enzyme exists in an intermediate quaternary state, ligation of ATP transforms the mutant enzyme to the R-state, whereas CTP converts this enzyme to the T-state. Thus, this mutant is much more sensitive to heterotropic allosteric control than is the native enzyme. In this communication we propose a preliminary model based on new crystallographic results that heterotropic regulation occurs partly through control of the quaternary structure by these effectors, thus regulating catalysis.
Stevens
R C
RC
Gibbs Chemical Laboratory, Harvard University, Cambridge, Massachusetts 02138.
Lipscomb
W N
WN
D000494:Allosteric Regulation; D001221:Aspartate Carbamoyltransferase / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D046911:Macromolecular Substances; D011485:Protein Binding; D011487:Protein Conformation; D014961:X-Ray Diffraction
D046911:Macromolecular Substances; D001221:Aspartate Carbamoyltransferase