Purification, Crystallization and Preliminary X-ray Analysis of the Aspartate Aminotransferase of Plasmodium Falciparum

Overview

Journal Acta Crystallogr Sect F Struct Biol Cryst Commun

Date 2010 Apr 13

PMID 20383010

Citations 5

Authors

Rishabh Jain

Rositsa Jordanova

Ingrid B Muller

Carsten Wrenger

Matthew R Groves

Affiliations

Soon will be listed here.

Abstract

Aspartate aminotransferases (EC 2.6.1.1) catalyse the conversion of aspartate and alpha-ketoglutarate to oxaloacetate and glutamate in a reversible manner. Thus, the aspartate aminotransferase of Plasmodium falciparum (PfAspAT) plays a central role in the transamination of amino acids. Recent findings suggest that PfAspAT may also play a pivotal role in energy metabolism and the de novo biosynthesis of pyrimidines. While therapeutics based upon the inhibition of other proteins in these pathways are already used in the treatment of malaria, the advent of multidrug-resistant strains has limited their efficacy. The presence of PfAspAT in these pathways may offer additional opportunities for the development of novel therapeutics. In order to gain a deeper understanding of the function and role of PfAspAT, it has been expressed and purified to homogeneity. The successful crystallization of PfAspAT, the collection of a 2.8 A diffraction data set and initial attempts to solve the structure using molecular replacement are reported.

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