THE IDEAL ALLOSTERIC ENZYME. William N. Lipscomb, Harvard University, Cambridge, MA

Structures for the T and R forms of dimeric chorismate mutase indicate a very simple allosteric mechanism for activation by tryptophan and inhibition by tyrosine. These allosteric effectors bind at the same allosteric sites some 20 Å and 30 Å away from the active sites of the dimer.

Activation by tryptophan is caused by its second ring which pushes apart the allosteric domain of one monomer, A, from the long helix of the other monomer, B. This helix connects to the active site of the other monomer, thus loosening the structure allowing binding residues to converge onto the substrate.

Inhibition by tyrosine, which tightens the enzyme, is promoted by its smalleraromatic ring, and especially by hydrogen bonds between its OH group and ThrB145 (of helix H8, chain B) and Arg A76 (of helix H5, chain A). Phenylalaninedoes not form these two hydrogen bonds and is not an effector.

Catalysis involves a hydrogen bond, or proton donation, to the oxygen of the enolpyruvate part of the substrate, a new mechanism unlike that in other chorismate mutases.

Reference:

N. Sträter, K. Håkansson, G. Schnappauf, G. Braus and W. N.Lipscomb, Proc. Natl. Acad. Sci. USA 93, 3330 (1996).