3PNR

Structure of PbICP-C in complex with falcipain-2

Summary for 3PNR

• Entry DOI: 10.2210/pdb3pnr/pdb
• Descriptor: Falcipain 2, PbICP-C, GLYCEROL, ... (5 entities in total)
• Functional Keywords: immunoglobulin fold, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Plasmodium falciparum; More
• Total number of polymer chains: 2
• Total formula weight: 48771.57

Authors

Hansen, G.,Hilgenfeld, R. (deposition date: 2010-11-19, release date: 2011-07-27, Last modification date: 2023-09-06)

Primary citation

Hansen, G.,Heitmann, A.,Witt, T.,Li, H.,Jiang, H.,Shen, X.,Heussler, V.T.,Rennenberg, A.,Hilgenfeld, R.
Structural basis for the regulation of cysteine-protease activity by a new class of protease inhibitors in Plasmodium.
Structure, 19:919-929, 2011

PubMed Abstract: Plasmodium cysteine proteases are essential for host-cell invasion and egress, hemoglobin degradation, and intracellular development of the parasite. The temporal, site-specific regulation of cysteine-protease activity is a prerequisite for survival and propagation of Plasmodium. Recently, a new family of inhibitors of cysteine proteases (ICPs) with homologs in at least eight Plasmodium species has been identified. Here, we report the 2.6 Å X-ray crystal structure of the C-terminal, inhibitory domain of ICP from P. berghei (PbICP-C) in a 1:1 complex with falcipain-2, an important hemoglobinase of Plasmodium. The structure establishes Plasmodium ICP as a member of the I42 class of chagasin-like protease inhibitors but with large insertions and differences in the binding mode relative to other family members. Furthermore, the PbICP-C structure explains why host-cell cathepsin B-like proteases and, most likely, also the protease-like domain of Plasmodium SERA5 (serine-repeat antigen 5) are no targets for ICP.

PubMed: 21742259
DOI: 10.1016/j.str.2011.03.025

Experimental method

X-RAY DIFFRACTION (2.6 Å)