期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：6
页码：2868-2873
DOI：10.1073/pnas.95.6.2868
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
