{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T01:06:22Z","timestamp":1778547982590,"version":"3.51.4"},"reference-count":60,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,11,20]],"date-time":"2015-11-20T00:00:00Z","timestamp":1447977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Indian Council of Research (ICMR), New Delhi, India"},{"name":"University Grants Commission (UGC), New Delhi, India"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2016,2]]},"abstract":"Summary<\/jats:title>Protein modification by ubiquitin (U<\/jats:styled-content>b) and U<\/jats:styled-content>b\u2010like molecules (U<\/jats:styled-content>bls) is a diverse biological process that regulates the activity of the target proteins. Systematic studies of U<\/jats:styled-content>bls in trypanosomatids like L<\/jats:italic><\/jats:styled-content>eishmania<\/jats:italic>, the causative organism of potentially fatal visceral leishmaniasis, would yield a better understanding of the disease pathogenesis and identify novel therapeutic targets. The present study is the first to characterize L<\/jats:italic><\/jats:styled-content>eishmania donovani<\/jats:italic>\u2010specific U<\/jats:styled-content>b\u2010related modifier\u20101 (LdU<\/jats:styled-content>rm1) and the associated conjugation pathway. Based on homology modeling, LdUrm1 was found to possess a \u03b2\u2010grasp fold and a C<\/jats:styled-content>\u2010terminal di\u2010glycine motif unique to U<\/jats:styled-content>b\/U<\/jats:styled-content>bls, essential for its conjugation to the target proteins. We identified LdU<\/jats:styled-content>ba4 as the E<\/jats:styled-content>1 enzyme for LdU<\/jats:styled-content>rm1 and demonstrated its energy\u2010dependent enzymatic activity. LdUrm1 was immunolocalized anteriorly near the flagellar reservoir, while LdUba4 was cytoplasmic, both in promastigotes and axenic amastigotes. Expression of nonconjugatable LdU<\/jats:styled-content>rm1 in L<\/jats:italic><\/jats:styled-content>.\u2009donovani<\/jats:italic> resulted in depleted parasite growth suggesting its role in the pathogenesis. By mass spectrometry, we identified R<\/jats:styled-content>ab5, a known mediator of early endosome regulated hemoglobin endocytosis in L<\/jats:italic><\/jats:styled-content>eishmania<\/jats:italic>, as a target of LdU<\/jats:styled-content>rm1. Our data suggest that LdU<\/jats:styled-content>rm1 conjugation pathway may have a role in early endosome\u2010mediated heme uptake in L<\/jats:italic><\/jats:styled-content>eishmania<\/jats:italic> that may be explored as a drug target.<\/jats:p>","DOI":"10.1111\/mmi.13253","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T04:51:02Z","timestamp":1445316662000},"page":"597-610","source":"Crossref","is-referenced-by-count":13,"title":["L<\/i><\/scp>eishmania donovani<\/i>\u2010specific U<\/scp>b\u2010related modifier\u20101: an early endosome\u2010associated ubiquitin\u2010like conjugation in L<\/i><\/scp>eishmania donovani<\/i>"],"prefix":"10.1111","volume":"99","author":[{"given":"Vanila","family":"Sharma","sequence":"first","affiliation":[{"name":"National Institute of Pathology (ICMR) Safdarjang Hospital Campus New Delhi 110029 India"},{"name":"Symbiosis School of Biomedical Sciences Symbiosis International University Pune 412115 Maharashtra 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