3BPM

Crystal Structure of Falcipain-3 with Its inhibitor, Leupeptin

Summary for 3BPM

• Entry DOI: 10.2210/pdb3bpm/pdb
• Related: 1AIM 1YVB 2GHU 3BPF
• Related PRD ID: PRD_000216
• Descriptor: Cysteine protease falcipain-3, Leupeptin, SULFATE ION, ... (4 entities in total)
• Functional Keywords: falcipain, malaria, cysteine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Plasmodium falciparum; More
• Total number of polymer chains: 4
• Total formula weight: 56090.63

Authors

kerr, I.D.,Lee, J.H.,Brinen, L.S. (deposition date: 2007-12-18, release date: 2008-12-30, Last modification date: 2024-11-20)

Primary citation

Kerr, I.D.,Lee, J.H.,Pandey, K.C.,Harrison, A.,Sajid, M.,Rosenthal, P.J.,Brinen, L.S.
Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.
J.Med.Chem., 52:852-857, 2009

PubMed Abstract: Falcipain-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.

PubMed: 19128015
DOI: 10.1021/jm8013663

Experimental method

X-RAY DIFFRACTION (2.5 Å)