{"id":215,"date":"2020-04-16T18:00:24","date_gmt":"2020-04-16T22:00:24","guid":{"rendered":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/?p=215"},"modified":"2020-04-23T17:05:33","modified_gmt":"2020-04-23T21:05:33","slug":"combatting-antibiotic-resistance-structural-characterization-of-vim-and-ndm-mutants","status":"publish","type":"post","link":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/combatting-antibiotic-resistance-structural-characterization-of-vim-and-ndm-mutants\/","title":{"rendered":"C28: Combatting Antibiotic Resistance: Structural Characterization of VIM and NDM Mutants"},"content":{"rendered":"

Antibiotics have been essential to the development of modern medical practices and are often used as the first line of defense in most illnesses. However, a cause of increasing problems and concerns in the medical community is the development of antibiotic-resistance mechanisms in pathogenic bacteria. Some of the most worrying enzymes to emerge are metallo-beta-lactamases (MBLs) \u2013 specifically, New Delhi (NDM), Verona Integron-Encoded (VIM), and active-on-imipenem (IMP) metallo-Beta-Lactamases \u2013 that are able to hydrolyze antibiotics that harbor beta-lactam rings, thus deactivating these frequently prescribed medicines. The genes that encode for these enzymes are also capable of horizontal transfer, making the spread of antibiotic resistant bacteria a global threat. The goal of this project is to elucidate structures of these metallo-beta-lactamases both in isolation and in complex with small molecule inhibitors in order to find specific and potent metallo-beta-lactamase inhibitors, allowing restoration of activity to beta-lactam antibiotics. Three mutations of both VIM (2, 20, and 31) and NDM (1, 4, 12, and later, X) metallo-beta-lactamases were chosen for crystallographic studies due to their propensity to crystallize with inhibitory molecules bound in their active sites, and due to their ability to withstand a large variety and concentration of antibiotics in and out of the presence of zinc. Due to interest in these enzymes’ ability to function even in low concentrations of zinc, a variant of New Delhi Metallo-beta-lactamase was constructed, a mono-zinc mutant (NDMX) that may provide insight on the mechanisms of these proteins preceding the execution of their hydrolyzing mechanisms.<\/p>\n

Authors: <\/strong>Matthew Morris & Matthew Orischak<\/p>\n

Faculty Advisor: <\/strong>Dr. Rick Page, Department of Chemistry & Biochemistry<\/p>\n

Graduate Student Advisor: <\/strong>Ben Shurina, Department of Chemistry & Biochemistry<\/p>\n\n\n

\"\"<\/figure>\n","protected":false},"excerpt":{"rendered":"

Antibiotics have been essential to the development of modern medical practices and are often used as the first line of defense in most illnesses. However, a cause of increasing problems and concerns in the medical community is the development of antibiotic-resistance mechanisms in pathogenic bacteria. Some of the most worrying enzymes to emerge are metallo-beta-lactamases […]<\/p>\n","protected":false},"author":2899,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_feature_clip_id":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"jetpack_post_was_ever_published":false},"categories":[10,27],"tags":[176,89],"class_list":["post-215","post","type-post","status-publish","format-standard","hentry","category-2020-posters","category-chemistry-biochemistry","tag-antibiotics","tag-stem"],"aioseo_notices":[],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/pbRpLx-3t","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/wp-json\/wp\/v2\/posts\/215","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/wp-json\/wp\/v2\/users\/2899"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/wp-json\/wp\/v2\/comments?post=215"}],"version-history":[{"count":0,"href":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/wp-json\/wp\/v2\/posts\/215\/revisions"}],"wp:attachment":[{"href":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/wp-json\/wp\/v2\/media?parent=215"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/wp-json\/wp\/v2\/categories?post=215"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.miamioh.edu\/undergraduate-research-forum\/wp-json\/wp\/v2\/tags?post=215"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}