1p9b
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Structure of fully ligated Adenylosuccinate synthetase from Plasmodium falciparum
OverviewOverview
In the absence of the de novo purine nucleotide biosynthetic pathway in, parasitic protozoa, purine salvage is of primary importance for parasite, survival. Enzymes of the salvage pathway are, therefore, good targets for, anti-parasitic drugs. Adenylosuccinate synthetase (AdSS), catalysing the, first committed step in the synthesis of AMP from IMP, is a potential, target for anti-protozoal chemotherapy. We report here the crystal, structure of adenylosuccinate synthetase from the malaria parasite, Plasmodium falciparum, complexed to 6-phosphoryl IMP, GDP, Mg2+ and the, aspartate analogue, hadacidin at 2 A resolution. The overall architecture, of P. falciparum AdSS (PfAdSS) is similar to the known structures from, Escherichia coli, mouse and plants. Differences in substrate interactions, seen in this structure provide a plausible explanation for the kinetic, differences between PfAdSS and the enzyme from other species. Additional, hydrogen bonding interactions of the protein with GDP may account for the, ordered binding of substrates to the enzyme. The dimer interface of PfAdSS, is also different, with a pronounced excess of positively charged, residues. Differences highlighted here provide a basis for the design of, species-specific inhibitors of the enzyme.
About this StructureAbout this Structure
1P9B is a Single protein structure of sequence from Plasmodium falciparum with MG, NO3, IMO, HDA and GDP as ligands. Active as Adenylosuccinate synthase, with EC number 6.3.4.4 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of fully ligated adenylosuccinate synthetase from Plasmodium falciparum., Eaazhisai K, Jayalakshmi R, Gayathri P, Anand RP, Sumathy K, Balaram H, Murthy MR, J Mol Biol. 2004 Jan 30;335(5):1251-64. PMID:14729341
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