{"90871":{"#nid":"90871","#data":{"type":"event","title":"(10-0914) Prof. Carla Mattos, NC State University","body":[{"value":"\u003Cp\u003EProf. Carla Mattos, North Carolina State University\n\u003C\/p\u003E\n\u003Cp\u003EIntrinsic hydrolysis in Ras functions through an allosteric switch in the Ras\/Raf\/MEK\/ERK signal transduction pathway\n\u003C\/p\u003E\n\u003Cp\u003EBiochemistry Seminar Series\n\u003C\/p\u003E\n\u003Cp\u003ERas is a key protein in cellular signal transduction. Mutants of G12 and Q61 impair GTPase activity and are found prominently in cancers. In wild type an allosteric switch promotes disorder to order transition in switch II, placing Q61 near water 189 in the active site. We show that the \u00e2\u0080\u009con\u00e2\u0080\u009d and \u00e2\u0080\u0098off\u00e2\u0080\u009d conformations of the allosteric switch can also be attained in RasG12V and RasQ61L. The \u00e2\u0080\u009con\u00e2\u0080\u009d state in both mutants disallows water 189 and proper placing of Q61 (or lack thereof). While the \u00e2\u0080\u009coff\u00e2\u0080\u009d state in RasG12V is disordered like wild type, that in RasQ61L stabilizes an anticatalytic conformation in the presence of Raf. Using a combination of structural analysis, hydrolysis rates in the presence and absence of Raf and experiments in NIH-3T3 cells we link the allosteric switch to the control of signaling in the Ras\/Raf\/MEK\/ERK pathway.  Furthermore, we have captured a transition state mimic for the intrinsic hydrolysis reaction using AlF\u003Csub\u003E3\u003C\/sub\u003E bound to an allosteric site mutant that stabilizes the \u00e2\u0080\u009con\u00e2\u0080\u009d state of the allosteric switch.\n\u003C\/p\u003E\n\u003Cp\u003EFor more information contact \u003Ca href=\u0022mailto:raquel.lieberman@chemistry.gatech.edu\u0022\u003EProf. Raquel Lieberman\u003C\/a\u003E (404-385-3663).\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"Prof. Carla Mattos, North Carolina State University\n\nIntrinsic hydrolysis in Ras functions through an allosteric switch in the Ras\/Raf\/MEK\/ERK signal transduction pathway\n\nBiochemistry Seminar Series","format":"limited_html"}],"field_summary_sentence":[{"value":"Prof. Carla Mattos, NC State University"}],"uid":"27275","created_gmt":"2010-03-03 01:00:00","changed_gmt":"2016-10-08 01:48:11","author":"Shirley Tomes","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2010-09-14T17:00:00-04:00","event_time_end":"2010-09-14T18:00:00-04:00","event_time_end_last":"2010-09-14T18:00:00-04:00","gmt_time_start":"2010-09-14 21:00:00","gmt_time_end":"2010-09-14 22:00:00","gmt_time_end_last":"2010-09-14 22:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"related_links":[{"url":"http:\/\/biochem.ncsu.edu\/faculty\/mattos\/mattos.htm","title":"Prof. Carla Mattos, North Carolina State University"}],"groups":[{"id":"85951","name":"School of Chemistry and Biochemistry"}],"categories":[],"keywords":[{"id":"919","name":"Biochemistry"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1795","name":"Seminar\/Lecture\/Colloquium"}],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cstrong\u003EShirley Tomes\u003C\/strong\u003E\u003Cbr \/\u003EChemistry \u0026amp; Biochemistry\u003Cbr \/\u003E\u003Ca href=\u0022http:\/\/www.gatech.edu\/contact\/index.html?id=st81\u0022\u003EContact Shirley Tomes\u003C\/a\u003E\u003Cbr \/\u003E\u003Cstrong\u003E404-894-0591\u003C\/strong\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}