title: Exploring the binding affinities of p300 enzyme activators CTPB and CTB using docking method.
abstract: CREB binding protein (CBP) and E1A binding protein p300, also known as p300 are functionally related transcriptional co-activators (CoAs) and histone acetyltransferases (HATs). Some small molecules, which target HATs can activate or inhibit the p300 enzyme potently. Here, we report the binding affinities of two small molecules CTPB [N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide] and CTB [N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxybenzamide] with p300 using docking method to obtain the insight of their interaction with p300. These small molecules bind to the enzyme, subsequently causing a structural change in the enzyme, which is responsible for the HAT activation. CTB exhibits higher binding affinity than CTPB, and their lowest docked energies are -7.72, -1.18 kcal/mol, respectively. In CTPB molecule, phenolic hydroxyl of Tyr1397 interacts with the non-polar atoms C(5E) and C(5F), and forms polar-non polar interactions. Similar interactions have also been observed in CTB. The residues Tyr1446 and Cys1438 interact with the non-pentadecyl atoms. Further, the docking study predicts a N-H--O hydrogen bonding interaction between CTB and Leu1398, in which the H--O contact distance is 2.06 A. The long pentadecyl chain of CTPB reduces the formation of hydrogen bond with the p300. The H-bond interaction could be the key factor for the better activation of CTB.
authors.affiliation: Laboratory of Biocrystallography and Computational Molecular Biology, Periyar University, Salem 636011, India.
authors.forename: B
authors.initials: B
authors.lastname: Devipriya
authors.forename: A Renuga
authors.initials: AR
authors.lastname: Parameswari
authors.forename: G
authors.initials: G
authors.lastname: Rajalakshmi
authors.forename: T
authors.initials: T
authors.lastname: Palvannan
authors.forename: P
authors.initials: P
authors.lastname: Kumaradhas
mesh_terms: D001549:Benzamides / Q000378:metabolism* / Q000494:pharmacology*; D001665:Binding Sites; D020134:Catalytic Domain; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D050880:p300-CBP Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D001549:Benzamides; D008024:Ligands; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C475167:N-(4-chloro-3-trifluoromethylphenyl)-2-ethoxy-6-pentadecylbenzamide