title: Separation of inhibition and activation of the allosteric yeast chorismate mutase.
abstract: Yeast chorismate mutase (EC 5.4.99.5) shows homotropic activation by the substrate, allosteric activation by tryptophan, and allosteric inhibition by tyrosine. In this study mutants of chorismate mutase have been found that remain sensitive to one allosteric effector (tryptophan) but insensitive to the other (tyrosine). These mutations are located in the catalytic domain: loop 220s (212-226) and helix 12 (227-251). The first example starts with the Thr-266 --> Ile mutant that had previously been shown to be locked in the activated R state. The additional mutation Ile-225 --> Thr unlocks the R state and restores the activation by tryptophan but not the inhibition by tyrosine. The second example refers to a molecular trigger for the switch between the T and R state: a hydrogen-bonded system, which stabilizes only the T state, from Tyr-234 to Glu-23 to Arg-157. Various mutants of Tyr-234, especially Tyr-234 --> Phe, are unresponsive to tyrosine but are activated by tryptophan. This separation of activation from inhibition may indicate a pathway for activation that is independent of the allosteric transition and may also be consistent with an intermediate structure between T and R states.
authors.affiliation: Institut für Mikrobiologie und Genetik, Georg-August-Universität, Grisebachstrasse 8, D-37077 Göttingen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Schnappauf
authors.forename: W N
authors.initials: WN
authors.lastname: Lipscomb
authors.forename: G H
authors.initials: GH
authors.lastname: Braus
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D002826:Chorismate Mutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D014364:Tryptophan / Q000494:pharmacology; D014443:Tyrosine / Q000494:pharmacology
chemical_list: D014443:Tyrosine; D014364:Tryptophan; D002826:Chorismate Mutase