Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi
- PMID: 17011790
- DOI: 10.1016/j.jsb.2006.07.017
Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi
Abstract
Trypanosoma cruzi chagasin belongs to a recently discovered family of cysteine protease inhibitors found in lower eukaryotes and prokaryotes but not in mammals. Chagasin binds tightly to cruzain, the major lysosomal T. cruzi cysteine protease, involved with infectivity and survival of the parasite in mammalian host cells. In the scope of a project to characterize proteins diferentially expressed during T. cruzi metacyclogenesis, we have determined the crystal structure of chagasin, which is now the first X-ray structure of a chagasin-like cysteine protease inhibitor to be reported. The structure was solved by the SIRAS method and refined at 1.7A resolution and a comparison with the two NMR structures available revealed some differences in the loops involved in binding to cysteine proteases. The highly flexible loop 4 could be entirely modeled and residues 29-33 from loop 2 form a 3(10)-helix structure that may be important to stabilize the loop conformation. Chagasin crystal structure was docked to the highest resolution structure available of cruzain and a model of chagasin-cruzain interaction was analyzed. The knowledge of the chagasin crystal structure may contribute to the elucidation of the molecular mechanism involved in the inhibition of cruzain and other T. cruzi cysteine proteases.
Similar articles
-
The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family.Structure. 2007 May;15(5):535-43. doi: 10.1016/j.str.2007.03.012. Structure. 2007. PMID: 17502099
-
Solution structure and backbone dynamics of the Trypanosoma cruzi cysteine protease inhibitor chagasin.J Mol Biol. 2006 Apr 14;357(5):1511-21. doi: 10.1016/j.jmb.2006.01.064. Epub 2006 Feb 3. J Mol Biol. 2006. PMID: 16490204
-
Development of alpha-keto-based inhibitors of cruzain, a cysteine protease implicated in Chagas disease.Bioorg Med Chem. 2005 Mar 15;13(6):2141-56. doi: 10.1016/j.bmc.2004.12.053. Bioorg Med Chem. 2005. PMID: 15727867
-
Natural cysteine protease inhibitors in protozoa: Fifteen years of the chagasin family.Biochimie. 2016 Mar;122:197-207. doi: 10.1016/j.biochi.2015.11.002. Epub 2015 Nov 4. Biochimie. 2016. PMID: 26546840 Review.
-
Parasite cysteine proteinase interactions with alpha 2-macroglobulin or kininogens: differential pathways modulating inflammation and innate immunity in infection by pathogenic trypanosomatids.Immunobiology. 2006;211(1-2):117-25. doi: 10.1016/j.imbio.2005.10.014. Epub 2005 Dec 27. Immunobiology. 2006. PMID: 16446176 Review.
Cited by
-
Role of the Trypanosoma brucei natural cysteine peptidase inhibitor ICP in differentiation and virulence.Mol Microbiol. 2007 Nov;66(4):991-1002. doi: 10.1111/j.1365-2958.2007.05970.x. Epub 2007 Oct 17. Mol Microbiol. 2007. PMID: 17944830 Free PMC article.
-
Exoerythrocytic Plasmodium parasites secrete a cysteine protease inhibitor involved in sporozoite invasion and capable of blocking cell death of host hepatocytes.PLoS Pathog. 2010 Mar 26;6(3):e1000825. doi: 10.1371/journal.ppat.1000825. PLoS Pathog. 2010. PMID: 20361051 Free PMC article.
-
Targeting Cysteine Proteases and their Inhibitors to Combat Trypanosomiasis.Curr Med Chem. 2024;31(16):2135-2169. doi: 10.2174/0929867330666230619160509. Curr Med Chem. 2024. PMID: 37340748 Review.
-
Inhibitor of cysteine proteases is critical for motility and infectivity of Plasmodium sporozoites.mBio. 2013 Nov 26;4(6):e00874-13. doi: 10.1128/mBio.00874-13. mBio. 2013. PMID: 24281719 Free PMC article.
-
The role of conserved residues of chagasin in the inhibition of cysteine peptidases.FEBS Lett. 2008 Feb 20;582(4):485-90. doi: 10.1016/j.febslet.2008.01.008. Epub 2008 Jan 15. FEBS Lett. 2008. PMID: 18201565 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
