{"entity": "publication", "iuid": "8268c516a3044af0a1ce9a783542a19c", "timestamp": "2026-08-11T07:54:24.332Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8268c516a3044af0a1ce9a783542a19c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8268c516a3044af0a1ce9a783542a19c"}}, "title": "Structure-guided design of novel thiazolidine inhibitors of O-acetyl serine sulfhydrylase from Mycobacterium tuberculosis.", "authors": [{"family": "Poyraz", "given": "Omer", "initials": "O"}, {"family": "Jeankumar", "given": "Variam Ullas", "initials": "VU"}, {"family": "Saxena", "given": "Shalini", "initials": "S"}, {"family": "Schnell", "given": "Robert", "initials": "R"}, {"family": "Haraldsson", "given": "Martin", "initials": "M"}, {"family": "Yogeeswari", "given": "Perumal", "initials": "P"}, {"family": "Sriram", "given": "Dharmarajan", "initials": "D"}, {"family": "Schneider", "given": "Gunter", "initials": "G"}], "type": "journal article", "published": "2013-08-22", "journal": {"title": "J. Med. Chem.", "issn": "0022-2623", "volume": "56", "issue": "16", "pages": "6457-6466", "issn-l": "0022-2623"}, "abstract": "The cysteine biosynthetic pathway is absent in humans but essential in microbial pathogens, suggesting that it provides potential targets for the development of novel antibacterial compounds. CysK1 is a pyridoxalphosphate-dependent O-acetyl sulfhydrylase, which catalyzes the formation of l-cysteine from O-acetyl serine and hydrogen sulfide. Here we report nanomolar thiazolidine inhibitors of Mycobacterium tuberculosis CysK1 developed by rational inhibitor design. The thiazolidine compounds were discovered using the crystal structure of a CysK1-peptide inhibitor complex as template. Pharmacophore modeling and subsequent in vitro screening resulted in an initial hit compound 2 (IC50 of 103.8 nM), which was subsequently optimized by a combination of protein crystallography, modeling, and synthetic chemistry. Hit expansion of 2 by chemical synthesis led to improved thiazolidine inhibitors with an IC50 value of 19 nM for the best compound, a 150-fold higher potency than the natural peptide inhibitor (IC50 2.9 \u03bcM).", "doi": "10.1021/jm400710k", "pmid": "23879381", "labels": {"Affiliated researcher": null}, "xrefs": [], "notes": [], "created": "2018-12-05T09:27:24.183Z", "modified": "2018-12-05T09:27:24.205Z"}