Hansen, G.; Heitmann, A.; Witt, T.; Li, H.; Jiang, H.; Shen, X.; Heussler, Volker; Rennenberg, A.; Hilgenfeld, R. (2011). Structural basis for the regulation of cysteine-protease activity by a new class of protease inhibitors in Plasmodium. Structure, 19(7), pp. 919-929. Cambridge, Mass.: Cell Press 10.1016/j.str.2011.03.025
Full text not available from this repository.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 A 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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Biology > Institute of Cell Biology 08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria |
UniBE Contributor: |
Heussler, Volker |
Subjects: |
500 Science > 570 Life sciences; biology |
ISSN: |
0969-2126 |
Publisher: |
Cell Press |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:27 |
Last Modified: |
05 Dec 2022 14:08 |
Publisher DOI: |
10.1016/j.str.2011.03.025 |
Web of Science ID: |
000292789300005 |
URI: |
https://boris.unibe.ch/id/eprint/10099 (FactScience: 215938) |
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