Structural Characterization of Histone Deacetylase from Plasmodium Falciparum
DOI:
https://doi.org/10.51983/ajsat-2012.1.2.733Keywords:
HDAC, Transcription regulation, molecular modelling, malaria, drug discoveryAbstract
Histone deacetylase (HDAC) is the key enzyme responsible for epigenetic regulation of an organism. This protein has been involved in transcriptional regulation of many proteins associated with chromatin remodelling. Homologs of histone deacetylase are also found in malaria parasite Plasmodium falciparum where it plays major role in regulation of key pathways of parasite. In this study, we determined the three-dimensional structure of histone deacetylase from Plasmodium falciparum (PfHDAC) by using homology modelling tools available at Swiss Modeller server and Modweb. Modelled structure was alidated using Ramachandran plot and active site determination was performed using CASTp. We believe that structural analysis of PfHDAC could be pivotal in discovering new drug like molecules against malaria parasite.
References
Li J. Lin Q., Wang W., Wade P., Wong J., “Specific targeting and constitutive association of histone deacetylase complexes during transcriptional repression”, Genes Dev, 2002, Vol. 16, pp. 687-692.
Dokmanovic M., Marks P.A., “Prospects: histone deacetylase inhibitors”, J Cell Biochem, 2005, Vol. 96, pp.293-304. [3] Lagger G., O’Carroll D., Rembold M., et al, “Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression”, EMBO J, 2002, Vol. 21, pp.2672-81.
Xu W., Parmigiani R., PA M., “Histone deacetylase inhibitors: molecular mechanism of action”, Oncogene, 2007, Vol. 26, pp. 5541- 52.
Bolden J.E., Peart M.J., Johnstone R.W., “Anticancer activities of histone deacetylase inhibitors”, Nat Rev Drug Discov, 2006, Vol. 5, pp.769-84.
Chaal B.K., Gupta A.P., Wastuwidyaningtyas B.D., Luah Y-H., Bozdech Z., “Histone Deacetylases Play a Major Role in the Transcriptional Regulation of the Plasmodium falciparum Life Cycle”, PLoS Pathog, 2010, Vol. 6, No.1.
Renom M.A., Stuart A., Fiser A., Sánchez R., Melo F. And Sali A., “Comparative protein structure modeling of genes and genomes,” Annu Rev Biophys Biomol Struct., Vol. 29, 2000, pp. 291-325.
Lovell S.C., Davis I.W., Arendall W.B., de Bakker P.I., Word J.M., Prisant M.G., Richardson J.S. and Richardson D.C., “Structure validation by Calpha geometry: phi,psi and Cbeta deviation,” Proteins., Vol. 15, No. 3, 2000, pp. 437-50.
Dundas J., et. al., “CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues”, Nucleic Acids Res., Vol. 34, 2006, pp. 116-118. 10.
Pettersen E.F., Goddard T.D., Huang C.C., Couch G.S., Greenblatt D.M., Meng E.C. and Ferrin TE, “UCSF Chimera - A Visualization System for Exploratory Research and Analysis,” J Comput Chem., Vol. 25, 2004, pp. 1605-1612.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2012 The Research Publication
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.