Title

Comparative protein modeling of spermidine synthase from Plasmodium falciparum: A potential target for anti-malarial drug therapy

Authors

Duvvuru Muni Rajasekhara Reddy*

Affiliation

Division of biology, University of Fribourg, Fribourg, Switzerland

Email

raja.duvvuru@unifr.ch; * Corresponding author

Article Type

Hypothesis

Date

received November 15, 2006; revised December 05, 2006; accepted December 15, 2006; published online December 23, 2006

Abstract

Malaria, caused by protozoan parasites of the genus Plasmodium, affects up to 500 million individuals and kills over 1 million people every year. The increasing resistance of the malaria parasites has enforced strategies for finding new drug targets. In recent years, enzymes associated with the polyamine metabolism have attracted attention as drug targets.  Cytosolic Plasmodium falciparum spermidine synthase (PfPAPT) is a potential target for antimalarial chemotherapy. Contrasting with the other enzymes involved in the parasite polyamine amine biosynthesis, little information is available about this enzyme, and its crystallographic structure is unknown yet. In this paper I propose a theoretical low-resolution 3D model for PfPAPT based on crystal structure of the Arabidopsis thaliana, by multiple alignment followed by intensive optimization; validation and dynamic simulations in water. Comparison between the active sites of PfPAPT and human PAPT revealed key differences that could be useful for the design of new selective inhibitors of Plasmodium PAPT.

Keywords

spermidine synthase; antimalarial drug; drug target; protein modeling

Citation

Edited by

P. Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.