Exploring the binding affinities of p300 enzyme activators CTPB and CTB using docking method
B Devipriya1, A Renuga Parameswari, G Rajalakshmi
1Laboratory of Biocrystallography and Computational Molecular Biology, Periyar University, Salem 636011, India.
Indian Journal of Biochemistry & Biophysics
|March 2, 2011
Summary
Two small molecules, CTPB and CTB, were docked with p300 to understand their HAT activation. CTB showed higher binding affinity and potential for better enzyme activation due to favorable hydrogen bonding.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- CREB binding protein (CBP) and E1A binding protein p300 (p300) are critical transcriptional co-activators and histone acetyltransferases (HATs).
- Small molecules targeting HATs can modulate p300 enzyme activity, offering therapeutic potential.
Purpose of the Study:
- To investigate the binding affinities and interaction insights of two small molecules, CTPB and CTB, with the p300 enzyme using molecular docking.
- To elucidate the structural basis for HAT activation by these small molecules.
Main Methods:
- Molecular docking simulations were employed to predict the binding modes and affinities of CTPB and CTB with p300.
- Analysis of intermolecular interactions, including hydrogen bonding and polar-nonpolar interactions, was performed.
Main Results:
- CTB demonstrated a significantly higher binding affinity to p300 compared to CTPB, with lowest docked energies of -7.72 kcal/mol for CTB and -1.18 kcal/mol for CTPB.
- Both molecules formed polar-nonpolar interactions with p300 residues. CTB formed a key hydrogen bond with Leu1398, while the pentadecyl chain of CTPB hindered such interactions.
Conclusions:
- CTB's superior binding affinity and hydrogen bonding capability suggest it is a more potent activator of p300 HAT activity.
- The structural insights gained can guide the design of novel p300-targeting therapeutics.
