{"668566":{"#nid":"668566","#data":{"type":"external_news","title":"Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein","body":[{"value":"\u003Cp\u003EMembrane efflux pumps play a major role in bacterial multidrug resistance. The tripartite multi-drug efflux pump system from\u0026nbsp;\u003Cem\u003EEscherichia coli\u003C\/em\u003E, AcrAB-TolC, is a target for inhibition to lessen resistance development and restore antibiotic efficacy, with homologs in other ESKAPE pathogens. Our results support a model where an inhibitor forms a molecular wedge within a cleft between the lipoyl and \u03b1\u03b2\u0026nbsp;barrel domains of AcrA, diminishing its conformational transmission of drug-evoked signals from AcrB to TolC. This work provides molecular insights into multi-drug adaptor protein function which could be valuable for developing antimicrobial therapeutics. Co-authors of the study include two \u003Ca href=\u0022https:\/\/chemistry.gatech.edu\u0022\u003ESchool of Chemistry and Biochemistry\u003C\/a\u003E researchers: Associate Professor\u0026nbsp;\u003Ca href=\u0022https:\/\/chemistry.gatech.edu\/people\/james-c-gumbart\u0022\u003EJames Gumbart\u003C\/a\u003E\u0026nbsp;and Ph.D. candidate \u003Ca href=\u0022https:\/\/www.linkedin.com\/in\/katie-m-kuo-1a9b4351\u0022\u003EKatie M. Kuo\u003C\/a\u003E.\u0026nbsp;(Gumbart is also an associate professor in the \u003Ca href=\u0022https:\/\/physics.gatech.edu\u0022\u003ESchool of Physics\u003C\/a\u003E.)\u0026nbsp;\u003C\/p\u003E\r\n","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EMembrane efflux pumps play a major role in bacterial multidrug resistance. The tripartite multi-drug efflux pump system from\u0026nbsp;\u003Cem\u003EEscherichia coli\u003C\/em\u003E, AcrAB-TolC, is a target for inhibition to lessen resistance development and restore antibiotic efficacy, with homologs in other ESKAPE pathogens. Our results support a model where an inhibitor forms a molecular wedge within a cleft between the lipoyl and \u03b1\u03b2\u0026nbsp;barrel domains of AcrA, diminishing its conformational transmission of drug-evoked signals from AcrB to TolC. This work provides molecular insights into multi-drug adaptor protein function which could be valuable for developing antimicrobial therapeutics. Co-authors of the study include two \u003Ca href=\u0022https:\/\/chemistry.gatech.edu\u0022\u003ESchool of Chemistry and Biochemistry\u003C\/a\u003E researchers: Associate Professor\u0026nbsp;\u003Ca href=\u0022https:\/\/chemistry.gatech.edu\/people\/james-c-gumbart\u0022\u003EJames Gumbart\u003C\/a\u003E\u0026nbsp;and Ph.D. candidate \u003Ca href=\u0022https:\/\/www.linkedin.com\/in\/katie-m-kuo-1a9b4351\u0022\u003EKatie M. Kuo\u003C\/a\u003E. (Gumbart is also an associate professor in the \u003Ca href=\u0022https:\/\/physics.gatech.edu\u0022\u003ESchool of Physics\u003C\/a\u003E.)\u0026nbsp;\u003C\/p\u003E\r\n","format":"limited_html"}],"field_summary_sentence":"","uid":"34434","created_gmt":"2023-07-24 15:32:09","changed_gmt":"2023-07-24 15:32:09","author":"Renay San Miguel","boilerplate_text":"","field_publication":"","publication":"Nature Communications ","field_article_url":"","publication_url":"https:\/\/www.nature.com\/articles\/s41467-023-39615-x","dateline":{"date":"2023-07-18T00:00:00-04:00","iso_date":"2023-07-18T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"groups":[{"id":"1278","name":"College of Sciences"},{"id":"85951","name":"School of Chemistry and Biochemistry"}],"categories":[{"id":"141","name":"Chemistry and Chemical Engineering"},{"id":"134","name":"Student and Faculty"}],"keywords":[{"id":"4896","name":"College of Sciences"},{"id":"166928","name":"School of Chemistry and Biochemistry"},{"id":"178909","name":"James Gumbart"},{"id":"192886","name":"Katie Kuo"},{"id":"178564","name":"bacterial resistance"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}