2H7W

Crystal structure of Chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi

Summary for 2H7W

• Entry DOI: 10.2210/pdb2h7w/pdb
• Descriptor: Chagasin (2 entities in total)
• Functional Keywords: beta-strands, immunoglobulin-fold, hydrolase inhibitor
• Biological source: Trypanosoma cruzi
• Cellular location: Flagellar pocket : Q966X9
• Total number of polymer chains: 2
• Total formula weight: 28958.15

Authors

Figueiredo da Silva, A.A.,Guimaraes, B.G. (deposition date: 2006-06-05, release date: 2006-10-10, Last modification date: 2024-02-14)

Primary citation

Figueiredo da Silva, A.A.,Vieira, L.C.,Krieger, M.A.,Goldenberg, S.,Zanchin, N.I.,Guimaraes, B.G.
Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi.
J.Struct.Biol., 157:416-423, 2007

PubMed 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.

PubMed: 17011790
DOI: 10.1016/j.jsb.2006.07.017

Experimental method

X-RAY DIFFRACTION (1.7 Å)