PMID: 8611180Feb 1, 1996Paper

Investigation of the substrate specificity of cruzipain, the major cysteine proteinase of Trypanosoma cruzi, through the use of cystatin-derived substrates and inhibitors

The Biochemical Journal
C ServeauF Gauthier

Abstract

A panel of intramolecularly quenched fluorogenic substrates containing the conserved QVVA and LVG inhibitory sequences of cystatin inhibitors was used to describe the specificity of the major cysteine proteinase of Trypanosoma cruzi (cruzipain or cruzain). This approach was based on the observations that: (1) cruzipain is strongly inhibited by chicken cystatin and rat T-kininogen, two representative members of cystatin families 2 and 3; (2) the QVVA- and LVG-containing substrates are specifically hydrolysed by papain-like proteinases; and (3) the cystatin-like motifs are similar to the proteolytically sensitive sequences in cruzipain that separate the pro-region and/or the C-terminal extension from the catalytic domain. Specificity constants (kcat/Km) were determined and compared with those of mammalian cathepsins B and L from rat liver lysosomes. Cruzipain and the mammalian proteinases cleaved cystatin-derived substrates at the same site, but their specificities differed significantly. Increased specificity for cruzipain was obtained by replacing amino acids at critical positions on both sides of the cleavage sites, especially at position P2'. The specificity constants (k(cat)/Km) obtained for the two substrates with a prolyl ...Continue Reading

Citations

Jul 11, 2002·Biological Chemistry·Gilles LalmanachEdith Authié
Jun 17, 2004·The Journal of Biological Chemistry·Angela L WilliamsonAlex Loukas
Feb 26, 2008·Biochemistry. Biokhimii︠a︡·G N Rudenskaya, D V Pupov
Sep 17, 1998·The Journal of Biological Chemistry·G LalmanachF Gauthier
Nov 5, 1997·The Journal of Biological Chemistry·E Del NeryL Juliano
Sep 22, 2010·PLoS Neglected Tropical Diseases·Yen Ting ChenWilliam R Roush
Sep 2, 2020·Pharmaceuticals·Ana Paula A DagninoRodrigo B M Silva
Dec 21, 2002·European Journal of Biochemistry·Claire DesmazesGilles Lalmanach
Jun 5, 2002·Annual Review of Biochemistry·Michael Klemba, Daniel E Goldberg
Sep 8, 2011·The Journal of Biological Chemistry·Florian VeillardGilles Lalmanach
Mar 27, 1999·FEBS Letters·F LecailleG Lalmanach
May 13, 2005·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Ken HirotsuIkuko Miyahara
Aug 1, 1997·Protein Science : a Publication of the Protein Society·S A GillmorR J Fletterick
Jun 23, 2010·Experimental Parasitology·Simone A KikuchiOctavio Fernandes
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Jul 1, 1997·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·C Kawabata, E Ichishima
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Oct 21, 2011·Journal of Agricultural and Food Chemistry·Marie BourinSophie Rehault-Godbert
Jul 31, 2019·Journal of Medicinal Chemistry·Lorenzo CianniCarlos A Montanari
Feb 23, 2008·Experimental Parasitology·Moshira M F HelmyHoda Y Sabry

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