Deciphering the binding mode and mechanistic insights of pentadecylidenemalonate (1b) as activator of histone acetyltransferase PCAF

Abstract

Histone acetyltransferases (HATs) is one among the conspicuous posttranslational modification in eukaryotic cells. p300/CBP Associated Factor (PCAF) and CREB-binding protein (CBP) are the two highly homologous HAT family which are vastly implicated in several diseases like cancer, diabetes, etc. Pentadecylidenemalonate, a simplified analog of anacardic acid, was reported as first mixed inhibitor/activator of HATs which inhibits p300/CBP and activates PCAF. It was appointed earlier as a valuable biological tool to understand the mechanism of lysine acetyltransferases due to its powerful apoptotic effect. In this study, pentadecylidenemalonate was taken for deciphering the binding mode, key interacting residues as well as mechanistic insights on PCAF and CBP as activator and inhibitor, respectively. This study is highly believed to help in rational design on antineoplastic drugs against PCAF.

Communicated by Ramaswamy H. Sarma

Keywords:

• Histone acetyltransferase
• PCAF
• CBP
• pentadecylidenemalonate
• molecular dynamics simulation

Acknowledgments

VS thanks Department of Science and Technology, Govt. of India for the INSPIRE senior research fellowship (No. DST/INSPIRE Fellowship/2012/482).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

SKS thank Department of Biotechnology, New Delhi, Govt. of India for providing financial support (No. BT/PR8138/BID/7/458/2013).