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Indian Journal of Biochemistry and Biophysics (IJBB) >
IJBB Vol.47 [2010] >
IJBB Vol.47(6) [December 2010] >
| Title: | Exploring the binding affinities of p300 enzyme activators CTPB and CTB using docking method |
| Authors: | Devipriya, B
Parameswari, A Renuga
Rajalakshmi, G
Palvannan, T
Kumaradhas, P |
| Keywords: | Binding affinity
p300
CTPB
CTB
Docking
Hydrogen bonding interaction |
| Issue Date: | Dec-2010 |
| Publisher: | NISCAIR-CSIR, India |
| 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-ethoxy-benzamide] 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 HO contact distance is 2.06 Å.
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. |
| Page(s): | 364-369 |
| CC License: |  CC Attribution-Noncommercial-No Derivative Works 2.5 India |
| ISSN: | 0975-0959 (Online); 0301-1208 (Print) |
| Source: | IJBB Vol.47(6) [December 2010]
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