3ebg | pdb_00003ebg

Structure of the M1 Alanylaminopeptidase from malaria

spinqualitylabelsall models 3ebg, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ebg is a 1 chain structure with sequence from Plafq. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, MG, ZN Related: 3ebh, 3ebi Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [AMP1_PLAFQ] Displays aminopeptidase activity with a broad substrate specificity. Preferentially hydrolyzes L-Lys-AMC but also shows strong activity against L-Ala-AMC, L-Arg-AMC and L-Leu-AMC. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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[CH(2)]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. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase.,McGowan S, Porter CJ, Lowther J, Stack CM, Golding SJ, Skinner-Adams TS, Trenholme KR, Teuscher F, Donnelly SM, Grembecka J, Mucha A, Kafarski P, Degori R, Buckle AM, Gardiner DL, Whisstock JC, Dalton JP Proc Natl Acad Sci U S A. 2009 Feb 5. PMID:19196988 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminopeptidase

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