3bpm | pdb_00003bpm
Crystal Structure of Falcipain-3 with Its inhibitor, Leupeptin
Structural highlights
FunctionFPC3_PLAF7 Cysteine protease which cleaves native host hemoglobin and globin in the food vacuole during the asexual blood stage (PubMed:11716777, PubMed:19357776). Preferentially cleaves substrates which have an arginine at the P1 position and a leucine at the P2 position (PubMed:19357776).[1] [2] 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 PubMedFalcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes. Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.,Kerr ID, Lee JH, Pandey KC, Harrison A, Sajid M, Rosenthal PJ, Brinen LS J Med Chem. 2009 Feb 12;52(3):852-7. PMID:19128015[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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