Activation of p300 histone acetyltransferase by small molecules altering enzyme structure: probed by surface-enhanced Raman Spectroscopy

Mantelingu, K. and Kishore, A. Hari and Balasubramanyam, K. and Pavan Kumar, G. V. and Altaf, M. and Nanjunda Swamy, S. and Selvi, Ruthrotha and Das, Chandrima and Narayana, Chandrabhas and Rangappa, K. S. and Kundu, Tapas K. (2007) Activation of p300 histone acetyltransferase by small molecules altering enzyme structure: probed by surface-enhanced Raman Spectroscopy. The Journal of Physical Chemistry B, 111 (17). pp. 4527-4534. ISSN 1520-5207

[img] Text (Full Text)
Activation of p300 Histone Acetyltransferase.pdf - Published Version
Restricted to Registered users only

Download (412kB) | Request a copy
Official URL: https://doi.org/10.1021/jp067655s

Abstract

Reversible acetylation of nucleosomal histones and nonhistone proteins play pivotal roles in the regulation of all the DNA templated phenomenon. Dysfunction of the enzymes involved in the acetylation/deacetylation leads to several diseases. Therefore, these enzymes are the targets for new generation therapeutics. Here, we report the synthesis of trifluoromethyl phenyl benzamides and their effect on histone acetyltransferase (HAT) activity of p300. One of these benzamides, CTPB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), was discovered as a potent activator of the p300 HAT activity. We have found that pentadecyl hydrocarbon chain of CTPB is required to activate the HAT only under certain context. Furthermore, our results show that the relative position of −CF3 and −Cl in CTB (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide) is also very critical for the activation. Surface-enhanced Raman spectroscopy (SERS) of p300 and the HAT activator complexes evidently suggest that the activation of HAT activity is achieved by the alteration of p300 structure. Therefore, apart from elucidating the chemical basis for small molecule mediated activation of p300, this report also describes, for the first time, Raman spectroscopic analysis of the complexes of histone-modifying enzymes and their modulators, which may be highly useful for therapeutic applications.

Item Type: Article
Additional Information: PMID: 17417897
Subjects: C Chemical Science > Chemistry
Divisions: Department of > Chemistry
Depositing User: MUL SWAPNA user
Date Deposited: 26 Sep 2019 10:36
Last Modified: 26 Sep 2019 10:36
URI: http://eprints.uni-mysore.ac.in/id/eprint/8570

Actions (login required)

View Item View Item