{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T12:48:56Z","timestamp":1788526136817,"version":"build-2803163510"},"reference-count":120,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science and Engineering Research Council of Canada (NSERC)","award":["04840-2018"],"award-info":[{"award-number":["04840-2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cysteine, a semi-essential amino acid, is found in the active site of a number of vital enzymes of the bacterium Mycobacterium tuberculosis (Mtb) and in particular those that relate to its survival, adaptability and pathogenicity. Mtb is the causative agent of tuberculosis, an infectious disease that affects millions of people globally. Common anti-tuberculosis targets are focused on immobilizing a vital cysteine amino acid residue in enzymes that plays critical roles in redox and non-redox catalysis, the modulation of the protein, enzyme activity, protein structure and folding, metal coordination, and posttranslational modifications of newly synthesized proteins. This review examines five Mtb enzymes that contain an active site cysteine residue and are considered as key targets for anti-tuberculosis drugs, namely alkyl hydroperoxide reductase (AhpC), dihydrolipoamide dehydrogenase (Lpd), aldehyde dehydrogenase (ALDH), methionine aminopeptidase (MetAP) and cytochromes P450. AhpC and Lpd protect Mtb against oxidative and nitrosative stress, whereas AhpC neutralizes peroxide\/peroxynitrite substrates with two active site cysteine residues. Mtb ALDH detoxifies aldehydes, using a nucleophilic active site cysteine to form an oxyanion thiohemiacetal intermediate, whereas MtMetAP\u2019s active site cysteine is essential for substrate recognition. The P450s metabolize various endogenous and exogenous compounds. Targeting these critical active site cysteine residues could disrupt enzyme functions, presenting a promising avenue for developing anti-mycobacterial agents.<\/jats:p>","DOI":"10.3390\/ijms26083845","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T06:23:56Z","timestamp":1744957436000},"page":"3845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Insights into Active Site Cysteine Residues in Mycobacterium tuberculosis Enzymes: Potential Targets for Anti-Tuberculosis Intervention"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6989-0342","authenticated-orcid":false,"given":"Abayomi S.","family":"Faponle","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Basic Medical Sciences, Sagamu Campus, Olabisi Onabanjo University, Ago-Iwoye 120107, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-9781","authenticated-orcid":false,"given":"James W.","family":"Gauld","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada"},{"name":"Department of Chemistry, Memorial University of Newfoundland, St. John\u2019s, NL A1C 5S7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2620-8788","authenticated-orcid":false,"given":"Sam P.","family":"de Visser","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1126\/science.287.5462.2391a","article-title":"Infectious disease: Drug-resistant TB on the rise","volume":"287","author":"Stokstad","year":"2000","journal-title":"Science"},{"key":"ref_2","unstructured":"World Health Organization (WHO) (2024, October 24). \u201cTuberculosis (TB)\u201d 7 November 2023. 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