| http://purl.uniprot.org/citations/34664502 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34664502 | http://www.w3.org/2000/01/rdf-schema#comment | "The isocitrate lyase paralogs of Mycobacterium tuberculosis (ICL1 and 2) are essential for mycobacterial persistence and constitute targets for the development of antituberculosis agents. We report that (2R,3S)-2-hydroxy-3-(nitromethyl)succinic acid (5-NIC) undergoes apparent retro-aldol cleavage as catalyzed by ICL1 to produce glyoxylate and 3-nitropropionic acid (3-NP), the latter of which is a covalent-inactivating agent of ICL1. Kinetic analysis of this reaction identified that 5-NIC serves as a robust and efficient mechanism-based inactivator of ICL1 (kinact/KI = (1.3 ± 0.1) × 103 M-1 s-1) with a partition ratio <1. Using enzyme kinetics, mass spectrometry, and X-ray crystallography, we identified that the reaction of the 5-NIC-derived 3-NP with the Cys191 thiolate of ICL1 results in formation of an ICL1-thiohydroxamate adduct as predicted. One aspect of the design of 5-NIC was to lower its overall charge compared to isocitrate to assist with cell permeability. Accordingly, the absence of the third carboxylate group will simplify the synthesis of pro-drug forms of 5-NIC for characterization in cell-infection models of M. tuberculosis."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.org/dc/terms/identifier | "doi:10.1021/jacs.1c07970"xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/author | "Krieger I.V."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/author | "Sacchettini J.C."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/author | "Meek T.D."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/author | "Laganowsky A."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/author | "Harris L.D."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/author | "Torres D."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/author | "Cameron S.A."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/author | "Mellott D.M."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/author | "Moghadamchargari Z."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/name | "J Am Chem Soc"xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/pages | "17666-17676"xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/title | "Mechanism-Based Inactivation of Mycobacterium tuberculosis Isocitrate Lyase 1 by (2R,3S)-2-Hydroxy-3-(nitromethyl)succinic acid."xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://purl.uniprot.org/core/volume | "143"xsd:string |
| http://purl.uniprot.org/citations/34664502 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34664502 |
| http://purl.uniprot.org/citations/34664502 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34664502 |
| http://purl.uniprot.org/uniprot/#_P9WKK7-mappedCitation-34664502 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34664502 |
| http://purl.uniprot.org/uniprot/P9WKK7 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/34664502 |