Please use this identifier to cite or link to this item: http://lib.jncasr.ac.in:8080/jspui/handle/10572/400
Title: Inhibition of Lysine Acetyltransferase KAT3B/p300 Activity by a Naturally Occurring Hydroxynaphthoquinone, Plumbagin
Authors: Ravindra, Kodihalli C
Selvi, B Ruthrotha
Arif, Mohammed
Reddy, B A Ashok
Thanuja, Gali R
Agrawal, Shipra
Pradhan, Suman Kalyan
Nagashayana, Natesh
Dasgupta, Dipak
Kundu, Tapas K
Keywords: P300 Histone Acetyltransferase
Enhanced Raman-Spectroscopy
Global Gene- Expression
Transcriptional Coactivator
Cancer Cells
Chromatin Transcription
Protein Acetylation
Small Molecules
Human-Disease
Dna-Damage
Issue Date: 4-Sep-2009
Publisher: American Society for Biochemistry and Molecular Biology Inc
Citation: Journal Of Biological Chemistry 284(36), 24453-24464 (2009)
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.
Description: Restricted Access
URI: http://hdl.handle.net/10572/400
Other Identifiers: 0021-9258
Appears in Collections:Research Papers (Tapas K. Kundu)

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