Structural highlights
FunctionPublication Abstract from PubMedMalaria is one of the world's most prevalent parasitic diseases, with over 200 million cases annually. Alarmingly, the spread of drug-resistant parasites threatens the effectiveness of current antimalarials, and has made the development of novel therapeutic strategies a global health priority. Malaria parasites have a complicated lifecycle involving an asymptomatic 'liver stage' and a symptomatic 'blood stage'. During the blood stage, the parasites utilise a proteolytic cascade to digest host haemoglobin, which produces free amino acids absolutely necessary for parasite growth and reproduction. The enzymes required for haemoglobin digestion are therefore attractive therapeutic targets. The final step of the cascade is catalyzed by several metalloaminopeptidases (MAPs), including aminopeptidase P (APP). We developed a novel platform to examine the substrate fingerprint of APP from P. falciparum ( Pf APP), and show that it can catalyse the removal of any residue immediately prior to a proline. Further, we have determined the crystal structure of Pf APP, and present the first examination of the 3D structure of this essential malarial enzyme. Together, these analyses provide insight into potential mechanisms of inhibition that could be used to develop novel antimalarial therapeutics. Structure and Substrate Fingerprint of Aminopeptidase P from Plasmodium falciparum.,Drinkwater N, Kannan Sivaraman K, Bamert RS, Rut W, Mohamed K, Vinh NB, Scammells PJ, Drag M, McGowan S Biochem J. 2016 Jul 26. pii: BCJ20160550. PMID:27462122[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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