{"id":547,"date":"2018-10-15T13:19:23","date_gmt":"2018-10-15T13:19:23","guid":{"rendered":"https:\/\/www.mbc.manchester.ac.uk\/barrangroup\/?p=547"},"modified":"2019-07-08T09:44:14","modified_gmt":"2019-07-08T09:44:14","slug":"uncoupling-conformational-states-from-activity-in-an-allosteric-enzyme","status":"publish","type":"post","link":"https:\/\/www.mbc.manchester.ac.uk\/barrangroup\/2018\/10\/15\/uncoupling-conformational-states-from-activity-in-an-allosteric-enzyme\/","title":{"rendered":"Uncoupling conformational states from activity in an allosteric enzyme"},"content":{"rendered":"

ATP-phosphoribosyltransferase (ATP-PRT) is a hexameric enzyme in conformational equilibrium between an open and seemingly active state and a closed and presumably inhibited form. The structure-function relationship of allosteric regulation in this system is still not fully understood. Here, we develop a screening strategy for modulators of ATP-PRT and identify 3-(2-thienyl)-L-<\/span>alanine (TIH) as an allosteric activator of this enzyme. Kinetic analysis reveals co-occupancy of the allosteric sites by TIH and\u00a0L<\/span>-histidine. Crystallographic and native ion-mobility mass spectrometry data show that the TIH-bound activated form of the enzyme closely resembles the inhibited\u00a0L<\/span>-histidine-bound closed conformation, revealing the uncoupling between ATP-PRT open and closed conformations and its functional state. These findings suggest that dynamic processes are responsible for ATP-PRT allosteric regulation and that similar mechanisms might also be found in other enzymes bearing a ferredoxin-like allosteric domain.<\/p>\n

https:\/\/www.nature.com\/articles\/s41467-017-00224-0<\/a><\/p>\n

\"\"<\/p>\n

Jo\u00e3o P. Pisco, Cesira de Chiara, Kamila J. Pacholarz, Acely Garza-Garcia, Roksana W. Ogrodowicz, Philip A. Walker, Perdita E. Barran, Stephen J. Smerdon & Luiz Pedro S. de Carvalho<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

ATP-phosphoribosyltransferase (ATP-PRT) is a hexameric enzyme in conformational equilibrium between an open and seemingly active state and a closed and presumably inhibited form. The structure-function relationship of allosteric regulation in this system is still not fully understood. Here, we develop a screening strategy for modulators of ATP-PRT and identify 3-(2-thienyl)-L-alanine (TIH) as an allosteric activator … <\/p>\n

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