OA:W2597859157<\/a><\/p>\nAuthors:<\/h4>\n
Narayan Prasad Sharma<\/p>\n
Abstract:<\/h4>\n
Zinc-containing metallo–lactamases(MLs) are an emerging class of enzymes that render bacteria resistant to -lactam-containing antibiotics, and these enzymes have been grouped into 3 distinct classes, B1, B2 and B3.While extensive structure\/mechanistic information is known about the B1 and B3 MLs, relatively little is known about the B2 enzymes.In an effort to characterize a B2 ML, spectroscopic and mechanistic studies on metallo–lactamase ImiS from Aeromonas bv.sobria, were performed. 1H NMR, UV-Vis, EPR, and EXAFS spectroscopic studies on Co(II)substituted ImiS revealed that the active site metal ion is tetrahedrally-coordinated by 1 cysteine, 1 histidine, and 1 aspartic acid and presumably 1 water ligands.Steady-state, presteady-state kinetic studies were conducted on ImiS and its reaction with imipenem and meropenem.pH Dependence studies revealed no inflection points in the pH range 5.0-8.5, while proton inventories demonstrated at least 1 rate-limiting proton transfer.Stopped-flow fluorescence, stopped-flow UV-Vis, and rapid freeze quench EPR studies on Co(II)-substituted ImiS revealed a kinetic mechanism in which the rate-limiting step is C-N bond cleavage.Site-directed spin labeling and EPR spectroscopy have revealed the movement of -helix in kinetically competent time scale.Taken together, this dissertation offers, the only structural and mechanistic information on a B2 ML and a common rate-limiting step for all ML’s that can be used to guide future inhibitor design efforts.Hawes, and Rio-Tsonis for their helpful suggestions and support of my studies at Miami University.Additionally, I would also like to thank my friends Drs.Tara Sigdel and Janardan Subedi and their families for being supportive to me during my stay at Oxford. Thanks also go to Christine Hajdin<\/p>\n","protected":false},"excerpt":{"rendered":"
DOI: OA:W2597859157 Authors: Narayan Prasad Sharma Abstract: Zinc-containing metallo–lactamases(MLs) are an emerging class of enzymes that render bacteria resistant to -lactam-containing antibiotics, and these enzymes have been grouped into 3 distinct classes, B1, B2 and B3.While extensive structure\/mechanistic information is known about the B1 and B3 MLs, relatively little is known about the B2 enzymes.In […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5],"tags":[],"class_list":["post-530","post","type-post","status-publish","format-standard","hentry","category-freeze-quench"],"_links":{"self":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/530","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=530"}],"version-history":[{"count":0,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/530\/revisions"}],"wp:attachment":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=530"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=530"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=530"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}