This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1p9b
From Proteopedia
Structure of fully ligated Adenylosuccinate synthetase from Plasmodium falciparum
Overview
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 Structure
1P9B is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 04:50:43 2008
