Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase

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Show simple item record Mcgowan, Sheena en_US Porter, Corinne en_US Lowther, Jonathan en_US Stack, Colin en_US Golding, Sarah en_US Skinner-Adams, Tina en_US Trenholme, Katharine en_US Teuscher, Franka en_US Donnelly, Sheila en_US Grembecka, Jolanta en_US Mucha, Artur en_US Kafarski, Pawel en_US Degori, Ross en_US Buckle, Ashley en_US Gardiner, Donald en_US Whisstock, James en_US Dalton, John en_US
dc.contributor.editor en_US 2010-07-13T08:48:24Z 2010-07-13T08:48:24Z 2009 en_US
dc.identifier 2009005820 en_US
dc.identifier.citation Mcgowan Sheena et al. 2009, 'Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase', National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2537-2542. en_US
dc.identifier.issn 0027-8424 en_US
dc.identifier.other C1 en_US
dc.description.abstract Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH2]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite. en_US
dc.language en_US
dc.publisher National Academy of Sciences of the United States of America en_US
dc.relation.isbasedon en_US
dc.title Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase en_US
dc.parent Proceedings Of The National Academy Of Sciences Of The United States Of America en_US
dc.journal.volume 106 en_US
dc.journal.number 8 en_US
dc.publocation USA en_US
dc.identifier.startpage 2537 en_US
dc.identifier.endpage 2542 en_US SCI.Faculty of Science en_US
dc.conference Verified OK en_US
dc.for 060500 en_US
dc.personcode 0000041750 en_US
dc.personcode 0000062660 en_US
dc.personcode 996591 en_US
dc.personcode 995262 en_US
dc.personcode 0000062661 en_US
dc.personcode 0000027738 en_US
dc.personcode 0000022368 en_US
dc.personcode 0000032865 en_US
dc.personcode 995261 en_US
dc.personcode 0000022369 en_US
dc.personcode 0000032866 en_US
dc.personcode 0000032867 en_US
dc.personcode 0000062662 en_US
dc.personcode 0000062663 en_US
dc.personcode 0000022367 en_US
dc.personcode 0000041751 en_US
dc.personcode 030896 en_US
dc.percentage 100 en_US Microbiology en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US en_US
dc.location.activity en_US
dc.description.keywords drug design malaria structural biology protease en_US
dc.staffid 030896 en_US

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