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dc.contributor.authorBhowmick, Tuhin
dc.contributor.authorGhosh, Soumitra
dc.contributor.authorDixit, Karuna
dc.contributor.authorGanesan, Varsha
dc.contributor.authorRamagopal, Udupi A.
dc.contributor.authorDey, Debayan
dc.contributor.authorSarma, Siddhartha P.
dc.contributor.authorRamakumar, Suryanarayanarao
dc.contributor.authorNagaraja, V.
dc.date.accessioned2017-02-21T09:53:24Z-
dc.date.available2017-02-21T09:53:24Z-
dc.date.issued2014
dc.identifier.citationBhowmick, T; Ghosh, S; Dixit, K; Ganesan, V; Ramagopal, UA; Dey, D; Sarma, SP; Ramakumar, S; Nagaraja, V, Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors. Nature Communications 2014, 5, 4124 http://dx.doi.org/10.1038/ncomms5124en_US
dc.identifier.citationNature Communicationsen_US
dc.identifier.citation5en_US
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/10572/2601-
dc.descriptionRestricted Accessen_US
dc.description.abstractThe nucleoid-associated protein HU plays an important role in maintenance of chromosomal architecture and in global regulation of DNA transactions in bacteria. Although HU is essential for growth in Mycobacterium tuberculosis (Mtb), there have been no reported attempts to perturb HU function with small molecules. Here we report the crystal structure of the N-terminal domain of HU from Mtb. We identify a core region within the HU-DNA interface that can be targeted using stilbene derivatives. These small molecules specifically inhibit HU-DNA binding, disrupt nucleoid architecture and reduce Mtb growth. The stilbene inhibitors induce gene expression changes in Mtb that resemble those induced by HU deficiency. Our results indicate that HU is a potential target for the development of therapies against tuberculosis.en_US
dc.description.urihttp://dx.doi.org/10.1038/ncomms5124en_US
dc.language.isoEnglishen_US
dc.publisherNature Publishing Groupen_US
dc.rights@Nature Publishing Group, 2014en_US
dc.subjectResistant Tuberculosisen_US
dc.subjectMultidrug-Resistanten_US
dc.subjectAccurate Dockingen_US
dc.subjectDrug Discoveryen_US
dc.subjectTrans-Stilbeneen_US
dc.subjectDNAen_US
dc.subjectBindingen_US
dc.subjectGenesen_US
dc.subjectDatabaseen_US
dc.subjectBiologyen_US
dc.titleTargeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitorsen_US
dc.typeArticleen_US
Appears in Collections:Research Articles (Nagaraja, V.)

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