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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.S

Abstract

Protein inhibitors of proteolytic enzymes regulate proteolysis and prevent the pathological effects of excess endogenous or exogenous proteases. Cysteine proteases are a large family of enzymes found throughout the plant and animal kingdoms. Disturbance of the equilibrium between cysteine proteases and natural inhibitors is a key event in the pathogenesis of cancer, rheumatoid arthritis, osteoporosis, and emphysema. A family (I42) of cysteine protease inhibitors (http://merops.sanger.ac.uk) was discovered in protozoan parasites and recently found widely distributed in prokaryotes and eukaryotes. We report the 2.2 A crystal structure of the signature member of the I42 family, chagasin, in complex with a cysteine protease. Chagasin has a unique variant of the immunoglobulin fold with homology to human CD8alpha. Interactions of chagasin with a target protease are reminiscent of the cystatin family inhibitors. Protein inhibitors of cysteine proteases may have evolved more than once on nonhomologous scaffolds.

Links

Publisher Full Text
linkinghub.elsevier.com
linkinghub.elsevier.com

Authors+Show Affiliations

Wang SX
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Pandey KC
No affiliation info available
Scharfstein J
No affiliation info available
Whisstock J
No affiliation info available
Huang RK
No affiliation info available
Jacobelli J
No affiliation info available
Fletterick RJ
No affiliation info available
Rosenthal PJ
No affiliation info available
Abrahamson M
No affiliation info available
Brinen LS
No affiliation info available
Rossi A
No affiliation info available
Sali A
No affiliation info available
McKerrow JH
No affiliation info available

MeSH

Amino Acid SequenceAnimalsCysteine EndopeptidasesEvolution, MolecularMolecular Sequence DataMultigene FamilyProtease InhibitorsProtein BindingProtozoan ProteinsTrypanosoma cruzi

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17502099

Citation

Wang, Stephanie X., et al. "The Structure of Chagasin in Complex With a Cysteine Protease Clarifies the Binding Mode and Evolution of an Inhibitor Family." Structure (London, England : 1993), vol. 15, no. 5, 2007, pp. 535-43.
Wang SX, Pandey KC, Scharfstein J, et al. The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family. Structure. 2007;15(5):535-43.
Wang, S. X., Pandey, K. C., Scharfstein, J., Whisstock, J., Huang, R. K., Jacobelli, J., Fletterick, R. J., Rosenthal, P. J., Abrahamson, M., Brinen, L. S., Rossi, A., Sali, A., & McKerrow, J. H. (2007). The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family. Structure (London, England : 1993), 15(5), 535-43.
Wang SX, et al. The Structure of Chagasin in Complex With a Cysteine Protease Clarifies the Binding Mode and Evolution of an Inhibitor Family. Structure. 2007;15(5):535-43. PubMed PMID: 17502099.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family. AU - Wang,Stephanie X, AU - Pandey,Kailash C, AU - Scharfstein,Julio, AU - Whisstock,James, AU - Huang,Rick K, AU - Jacobelli,Jordan, AU - Fletterick,Robert J, AU - Rosenthal,Philip J, AU - Abrahamson,Magnus, AU - Brinen,Linda S, AU - Rossi,Andrea, AU - Sali,Andrej, AU - McKerrow,James H, PY - 2006/11/21/received PY - 2007/03/01/revised PY - 2007/03/20/accepted PY - 2007/5/16/pubmed PY - 2007/9/29/medline PY - 2007/5/16/entrez SP - 535 EP - 43 JF - Structure (London, England : 1993) JO - Structure VL - 15 IS - 5 N2 - Protein inhibitors of proteolytic enzymes regulate proteolysis and prevent the pathological effects of excess endogenous or exogenous proteases. Cysteine proteases are a large family of enzymes found throughout the plant and animal kingdoms. Disturbance of the equilibrium between cysteine proteases and natural inhibitors is a key event in the pathogenesis of cancer, rheumatoid arthritis, osteoporosis, and emphysema. A family (I42) of cysteine protease inhibitors (http://merops.sanger.ac.uk) was discovered in protozoan parasites and recently found widely distributed in prokaryotes and eukaryotes. We report the 2.2 A crystal structure of the signature member of the I42 family, chagasin, in complex with a cysteine protease. Chagasin has a unique variant of the immunoglobulin fold with homology to human CD8alpha. Interactions of chagasin with a target protease are reminiscent of the cystatin family inhibitors. Protein inhibitors of cysteine proteases may have evolved more than once on nonhomologous scaffolds. SN - 0969-2126 UR - https://www.unboundmedicine.com/medline/citation/17502099/The_structure_of_chagasin_in_complex_with_a_cysteine_protease_clarifies_the_binding_mode_and_evolution_of_an_inhibitor_family_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-2126(07)00120-7 DB - PRIME DP - Unbound Medicine ER -