{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T05:30:42Z","timestamp":1759815042547},"reference-count":66,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The endosymbiotic organism\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Wolbachia<\/jats:named-content>\n            is an attractive antifilarial drug target. Here we report on the cloning and expression of an\n            <jats:italic>rsmD<\/jats:italic>\n            -like rRNA methyltransferase from the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Wolbachia<\/jats:named-content>\n            endosymbiont of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brugia malayi<\/jats:named-content>\n            , its molecular properties, and assays for specific inhibitors. The gene was found to be expressed in all the major life stages of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. malayi<\/jats:named-content>\n            . The purified enzyme expressed in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            was found to be in monomer form in its native state. The activities of the specific inhibitors (heteroaryl compounds) against the enzyme were tested with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. malayi<\/jats:named-content>\n            adult and microfilariae for 7 days\n            <jats:italic>in vitro<\/jats:italic>\n            at various concentrations, and NSC-659390 proved to be the most potent compound (50% inhibitory concentration [IC\n            <jats:sub>50<\/jats:sub>\n            ], 0.32 \u03bcM), followed by NSC-658343 (IC\n            <jats:sub>50<\/jats:sub>\n            , 4.13 \u03bcM) and NSC-657589 (IC\n            <jats:sub>50<\/jats:sub>\n            , 7.5 \u03bcM). On intraperitoneal administration at 5 mg\/kg of body weight for 7 days to adult jirds into which\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. malayi<\/jats:named-content>\n            had been transplanted intraperitoneally, all the compounds killed a significant proportion of the implanted worms. A very similar result was observed in infected mastomys when inhibitors were administered. Docking studies of enzyme and inhibitors and an\n            <jats:italic>in vitro<\/jats:italic>\n            tryptophan quenching experiment were also performed to understand the binding mode and affinity. The specific inhibitors of the enzyme showed a higher affinity for the catalytic site of the enzyme than the nonspecific inhibitors and were found to be potent enough to kill the worm (both adults and microfilariae)\n            <jats:italic>in vitro<\/jats:italic>\n            as well as\n            <jats:italic>in vivo<\/jats:italic>\n            in a matter of days at micromolar concentrations. The findings suggest that these compounds be evaluated against other pathogens possessing a methyltransferase with a DPPY motif and warrant the design and synthesis of more such inhibitors.\n          <\/jats:p>","DOI":"10.1128\/aac.02264-12","type":"journal-article","created":{"date-parts":[[2013,6,4]],"date-time":"2013-06-04T00:46:00Z","timestamp":1370306760000},"page":"3843-3856","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Molecular Characterization of an\n            <i>rsmD<\/i>\n            -Like rRNA Methyltransferase from the Wolbachia Endosymbiont of Brugia malayi and Antifilarial Activity of Specific Inhibitors of the Enzyme"],"prefix":"10.1128","volume":"57","author":[{"given":"Ajay Kumar","family":"Rana","sequence":"first","affiliation":[{"name":"Division of Parasitology, Central Drug Research Institute, Lucknow, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharat","family":"Chandra","sequence":"additional","affiliation":[{"name":"Molecular and Structural Biology Division, Central Drug Research Institute, Lucknow, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Imran","family":"Siddiqi","sequence":"additional","affiliation":[{"name":"Molecular and Structural Biology Division, Central Drug Research Institute, Lucknow, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailja","family":"Misra-Bhattacharya","sequence":"additional","affiliation":[{"name":"Division of Parasitology, Central Drug Research Institute, Lucknow, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-4758(99)01533-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030121"},{"key":"e_1_3_3_4_2","volume-title":"Lymphatic filariasis","author":"WHO","year":"2011","unstructured":"WHO. 2011. 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