3kr5 | pdb_00003kr5

Structure of a protease 4

spinqualitylabelsall models 3kr5, resolution 2.56Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3kr5 is a 12 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.56Å Ligands: 1PE, BEY, CO3, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8IL11_PLAF7 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 Current therapeutics and prophylactics for malaria are under severe challenge as a result of the rapid emergence of drug-resistant parasites. The human malaria parasite Plasmodium falciparum expresses two neutral aminopeptidases, PfA-M1 and PfA-M17, which function in regulating the intracellular pool of amino acids required for growth and development inside the red blood cell. These enzymes are essential for parasite viability and are validated therapeutic targets. We previously reported the x-ray crystal structure of the monomeric PfA-M1 and proposed a mechanism for substrate entry and free amino acid release from the active site. Here, we present the x-ray crystal structure of the hexameric leucine aminopeptidase, PfA-M17, alone and in complex with two inhibitors with antimalarial activity. The six active sites of the PfA-M17 hexamer are arranged in a disc-like fashion so that they are orientated inwards to form a central catalytic cavity; flexible loops that sit at each of the six entrances to the catalytic cavern function to regulate substrate access. In stark contrast to PfA-M1, PfA-M17 has a narrow and hydrophobic primary specificity pocket which accounts for its highly restricted substrate specificity. We also explicate the essential roles for the metal-binding centers in these enzymes (two in PfA-M17 and one in PfA-M1) in both substrate and drug binding. Our detailed understanding of the PfA-M1 and PfA-M17 active sites now permits a rational approach in the development of a unique class of two-target and/or combination antimalarial therapy. Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases.,McGowan S, Oellig CA, Birru WA, Caradoc-Davies TT, Stack CM, Lowther J, Skinner-Adams T, Mucha A, Kafarski P, Grembecka J, Trenholme KR, Buckle AM, Gardiner DL, Dalton JP, Whisstock JC Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2449-54. Epub 2010 Jan 21. PMID:20133789 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminopeptidase 3D structures

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