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Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi.
J Struct Biol. 2007 Feb; 157(2):416-23.JS

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.

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Authors+Show Affiliations

Figueiredo da Silva AA
Centro de Biologia Molecular Estrutural, Laboratório Nacional de Luz Síncrotron, LNLS, P.O. Box 6192, CEP 13084-971, Campinas SP, Brazil.
de Carvalho Vieira L
No affiliation info available
Krieger MA
No affiliation info available
Goldenberg S
No affiliation info available
Zanchin NI
No affiliation info available
Guimarães BG
No affiliation info available

MeSH

Amino Acid SequenceAnimalsCrystallography, X-RayCysteine EndopeptidasesCysteine Proteinase InhibitorsModels, MolecularMolecular Sequence DataProtein BindingProtozoan ProteinsSequence Homology, Amino AcidTrypanosoma cruzi

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17011790

Citation

Figueiredo da Silva, Aline Almeida, et al. "Crystal Structure of Chagasin, the Endogenous Cysteine-protease Inhibitor From Trypanosoma Cruzi." Journal of Structural Biology, vol. 157, no. 2, 2007, pp. 416-23.
Figueiredo da Silva AA, de Carvalho Vieira L, Krieger MA, et al. Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi. J Struct Biol. 2007;157(2):416-23.
Figueiredo da Silva, A. A., de Carvalho Vieira, L., Krieger, M. A., Goldenberg, S., Zanchin, N. I., & Guimarães, B. G. (2007). Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi. Journal of Structural Biology, 157(2), 416-23.
Figueiredo da Silva AA, et al. Crystal Structure of Chagasin, the Endogenous Cysteine-protease Inhibitor From Trypanosoma Cruzi. J Struct Biol. 2007;157(2):416-23. PubMed PMID: 17011790.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Crystal structure of chagasin, the endogenous cysteine-protease inhibitor from Trypanosoma cruzi. AU - Figueiredo da Silva,Aline Almeida, AU - de Carvalho Vieira,Leandro, AU - Krieger,Marco Aurélio, AU - Goldenberg,Samuel, AU - Zanchin,Nilson Ivo Tonin, AU - Guimarães,Beatriz Gomes, Y1 - 2006/08/17/ PY - 2006/06/05/received PY - 2006/07/26/revised PY - 2006/07/28/accepted PY - 2006/10/3/pubmed PY - 2007/4/20/medline PY - 2006/10/3/entrez SP - 416 EP - 23 JF - Journal of structural biology JO - J Struct Biol VL - 157 IS - 2 N2 - 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. SN - 1047-8477 UR - https://www.unboundmedicine.com/medline/citation/17011790/Crystal_structure_of_chagasin_the_endogenous_cysteine_protease_inhibitor_from_Trypanosoma_cruzi_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1047-8477(06)00231-0 DB - PRIME DP - Unbound Medicine ER -