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Expanding the results of a high throughput screen against an isochorismate-pyruvate lyase to enzymes of a similar scaffold or mechanism
dc.contributor.author | Meneely, Kathleen M. | |
dc.contributor.author | Luo, Qianyi | |
dc.contributor.author | Riley, Andrew Philip | |
dc.contributor.author | Taylor, Byron | |
dc.contributor.author | Roy, Anuradha | |
dc.contributor.author | Stein, Ross L. | |
dc.contributor.author | Prisinzano, Thomas E. | |
dc.contributor.author | Lamb, Audrey L. | |
dc.date.accessioned | 2017-05-10T18:16:28Z | |
dc.date.available | 2017-05-10T18:16:28Z | |
dc.date.issued | 2014-11-01 | |
dc.identifier.citation | Meneely, K. M., Luo, Q., Riley, A. P., Taylor, B., Roy, A., Stein, R. L., … Lamb, A. L. (2014). Expanding the results of a high throughput screen against an isochorismate-pyruvate lyase to enzymes of a similar scaffold or mechanism. Bioorganic & Medicinal Chemistry, 22(21), 5961–5969. http://doi.org/10.1016/j.bmc.2014.09.010 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/24078 | |
dc.description.abstract | Antibiotic resistance is a growing health concern, and new avenues of antimicrobial drug design are being actively sought. One suggested pathway to be targeted for inhibitor design is that of iron scavenging through siderophores. Here we present a high throughput screen to the isochorismatepyruvate lyase of Pseudomonas aeruginosa, an enzyme required for the production of the siderophore pyochelin. Compounds identified in the screen are high nanomolar to low micromolar inhibitors of the enzyme and produce growth inhibition in PAO1 P. aeruginosa in the millimolar range under iron-limiting conditions. The identified compounds were also tested for enzymatic inhibition of E. coli chorismate mutase, a protein of similar fold and similar chemistry, and of Y. enterocolitica salicylate synthase, a protein of differing fold but catalyzing the same lyase reaction. In both cases, subsets of the inhibitors from the screen were found to be inhibitory to enzymatic activity (mutase or synthase) in the micromolar range and capable of growth inhibition in their respective organisms (E. coli or Y. enterocolitica). | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This article is made available under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) License. | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ | en_US |
dc.subject | Siderophore | en_US |
dc.subject | Isochorismate pyruvate lyase | en_US |
dc.subject | Chorismate mutase | en_US |
dc.subject | Salicylate synthase | en_US |
dc.title | Expanding the results of a high throughput screen against an isochorismate-pyruvate lyase to enzymes of a similar scaffold or mechanism | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Meneely, Kathleen M. | |
kusw.kuauthor | Luo, Qianyi | |
kusw.kuauthor | Lamb, Audrey L. | |
kusw.kuauthor | Riley, Andrew P. | |
kusw.kuauthor | Taylor, Byron | |
kusw.kuauthor | Roy, Anuradha | |
kusw.kuauthor | Stein, Ross L. | |
kusw.kuauthor | Prisinzano, Thomas E. | |
kusw.kudepartment | Molecular Biosciences | en_US |
kusw.kudepartment | Chemistry | en_US |
kusw.kudepartment | High Throughput Screening Facility | en_US |
kusw.kudepartment | Medicinal Chemistry | en_US |
dc.identifier.doi | 10.1016/j.bmc.2014.09.010 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC4254016 | en_US |
dc.rights.accessrights | openAccess |