3fnt | pdb_00003fnt

Crystal structure of pepstatin A bound histo-aspartic protease (HAP) from Plasmodium falciparum

spinqualitylabelsall models 3fnt, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3fnt is a 2 chain structure with sequence from Plasmodium falciparum 3D7 and Streptomyces argenteolus subsp. toyonakensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.3Å Ligands: EDO, IVA, STA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PLM3_PLAF7 During the asexual blood stage, catalyzes the cleavage of denatured host hemoglobin (Hb) or globins (PubMed:16624575). Digestion of host Hb is an essential step which provides the parasite with amino acids for protein synthesis, and regulates osmolarity (Probable). 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 The structures of recombinant histo-aspartic protease (HAP) from malaria-causing parasite Plasmodium falciparum as apoenzyme and in complex with two inhibitors, pepstatin A and KNI-10006, were solved at 2.5-, 3.3-, and 3.05-A resolutions, respectively. In the apoenzyme crystals, HAP forms a tight dimer not seen previously in any aspartic protease. The interactions between the monomers affect the conformation of two flexible loops, the functionally important "flap" (residues 70-83) and its structural equivalent in the C-terminal domain (residues 238-245), as well as the orientation of helix 225-235. The flap is found in an open conformation in the apoenzyme. Unexpectedly, the active site of the apoenzyme contains a zinc ion tightly bound to His32 and Asp215 from one monomer and to Glu278A from the other monomer, with the coordination of Zn resembling that seen in metalloproteases. The flap is closed in the structure of the pepstatin A complex, whereas it is open in the complex with KNI-10006. Although the binding mode of pepstatin A is significantly different from that in other pepsin-like aspartic proteases, its location in the active site makes unlikely the previously proposed hypothesis that HAP is a serine protease. The binding mode of KNI-10006 is unusual compared with the binding of other inhibitors from the KNI series to aspartic proteases. The novel features of the HAP active site could facilitate design of specific inhibitors used in the development of antimalarial drugs. Crystal structures of the histo-aspartic protease (HAP) from Plasmodium falciparum.,Bhaumik P, Xiao H, Parr CL, Kiso Y, Gustchina A, Yada RY, Wlodawer A J Mol Biol. 2009 May 8;388(3):520-40. Epub 2009 Mar 11. PMID:19285084 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Plasmepsin

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