{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:37Z","timestamp":1786977997205,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The emergence of multiple drug resistance and extreme drug resistance pathogens necessitates the continuous evaluation of the pathogenic genome to identify conserved molecular targets and their respective inhibitors. In this study, we mapped the global mutational landscape of\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    (an intracellular pathogen notoriously known to cause the sexually transmitted disease gonorrhoea). We identified highly variable amino acid positions in the antibiotic target genes like the\n                    <jats:italic>penA, ponA, 23s rRNA, rpoB, gyrA, parC, mtrR and porB<\/jats:italic>\n                    . Some variations are directly reported to confer resistance to the currently used front\u2010line drugs like ceftriaxone, cefixime, azithromycin\u00a0and ciprofloxacin. Further, by whole genome comparison and Shannon entropy analysis, we identified a completely conserved protein HtpX in the drug\u2010resistant as well as susceptible isolates of\n                    <jats:italic>N. gonorrhoeae<\/jats:italic>\n                    (NgHtpX). Comparison with the only available information of\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    HtpX suggested it to be a transmembrane metalloprotease having a role in stress response. The critical zinc\u2010binding residue of NgHtpX was mapped to E141. By applying composite high throughput screening followed by MD simulations, we identified pemirolast and thalidomide as high\u2010energy binding ligands of NgHtpX. Following cloning and expression of the purified metal\u2010binding domain of NgHtpX (NgHtpXd), its Zn\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010binding (K\n                    <jats:sub>d<\/jats:sub>\n                    \u2009=\u20090.4\u2009\u00b5M) and drug\u2010binding (pemirolast, K\n                    <jats:sub>d<\/jats:sub>\n                    \u2009=\u20093.47\u2009\u00b5M; and thalidomide, K\n                    <jats:sub>d<\/jats:sub>\n                    \u2009=\u20091.04\u2009\u00b5M) potentials were determined using in\u2010vitro fluorescence quenching experiment. When tested on\n                    <jats:italic>N. gonorrhoeae<\/jats:italic>\n                    cultures, both the ligands imposed a dose\u2010dependent reduction in viability. Overall, our results provide high entropy positions in the targets of presently used antibiotics, which can be further explored to understand the AMR mechanism. Additionally, HtpX and its specific inhibitors identified can be utilised effectively in managing gonococcal infections.\n                  <\/jats:p>","DOI":"10.1002\/jcb.30461","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T14:32:48Z","timestamp":1691764368000},"page":"1516-1529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evolutionarily conserved heat shock protein, HtpX, as an adjunct target against antibiotic\u2010resistant\n                    <i>Neisseria gonorrhoeae<\/i>"],"prefix":"10.1002","volume":"124","author":[{"given":"Shubham","family":"Vashishtha","sequence":"first","affiliation":[{"name":"Kusuma School of Biological Sciences Indian Institute of Technology Delhi New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetal","family":"Thakur","sequence":"additional","affiliation":[{"name":"Kusuma School of Biological Sciences 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