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Inhibition of Lysine Acetyltransferase KAT3B/p300 Activity by a Naturally Occurring Hydroxynaphthoquinone, Plumbagin

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dc.contributor.author Ravindra, Kodihalli C
dc.contributor.author Selvi, B Ruthrotha
dc.contributor.author Arif, Mohammed
dc.contributor.author Reddy, B A Ashok
dc.contributor.author Thanuja, Gali R
dc.contributor.author Agrawal, Shipra
dc.contributor.author Pradhan, Suman Kalyan
dc.contributor.author Nagashayana, Natesh
dc.contributor.author Dasgupta, Dipak
dc.contributor.author Kundu, Tapas K
dc.date.accessioned 2012-02-14T06:46:20Z
dc.date.available 2012-02-14T06:46:20Z
dc.date.issued 2009-09-04
dc.identifier 0021-9258 en_US
dc.identifier.citation Journal Of Biological Chemistry 284(36), 24453-24464 (2009) en_US
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/400
dc.description Restricted Access en_US
dc.description.abstract Lysine acetyltransferases (KATs), p300 (KAT3B), and its close homologue CREB-binding protein (KAT3A) are probably the most widely studied KATs with well documented roles in various cellular processes. Hence, the dysfunction of p300 may result in the dysregulation of gene expression leading to the manifestation of many disorders. The acetyltransferase activity of p300/CREB-binding protein is therefore considered as a target for new generation therapeutics. We describe here a natural compound, plumbagin (RTK1), isolated from Plumbago rosea root extract, that inhibits histone acetyltransferase activity potently in vivo. Interestingly, RTK1 specifically inhibits the p300-mediated acetylation of p53 but not the acetylation by another acetyltransferase, p300/CREB-binding protein-associated factor, PCAF, in vivo. RTK1 inhibits p300 histone acetyltransferase activity in a noncompetitive manner. Docking studies and site-directed mutagenesis of the p300 histone acetyltransferase domain suggest that a single hydroxyl group of RTK1 makes a hydrogen bond with the lysine 1358 residue of this domain. In agreement with this, we found that indeed the hydroxyl group-substituted plumbagin derivatives lost the acetyltransferase inhibitory activity. This study describes for the first time the chemical entity (hydroxyl group) required for the inhibition of acetyltransferase activity. en_US
dc.description.sponsorship Department of Biotechnology, Government of India. Jawaharlal Nehru Centre for Advanced Scientific Research. en_US
dc.description.uri http://dx.doi.org/10.1074/jbc.M109.023861 en_US
dc.language.iso en en_US
dc.publisher American Society for Biochemistry and Molecular Biology Inc en_US
dc.rights © 2009 The American Society for Biochemistry and Molecular Biology Inc en_US
dc.subject P300 Histone Acetyltransferase en_US
dc.subject Enhanced Raman-Spectroscopy en_US
dc.subject Global Gene- Expression en_US
dc.subject Transcriptional Coactivator en_US
dc.subject Cancer Cells en_US
dc.subject Chromatin Transcription en_US
dc.subject Protein Acetylation en_US
dc.subject Small Molecules en_US
dc.subject Human-Disease en_US
dc.subject Dna-Damage en_US
dc.title Inhibition of Lysine Acetyltransferase KAT3B/p300 Activity by a Naturally Occurring Hydroxynaphthoquinone, Plumbagin en_US
dc.type Article en_US


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