The role of conserved residues of chagasin in the inhibition of cysteine peptidases

dos Reis, F. C.G., Smith, B. O., Santos, C. C., Costa, T., F., Scharfstein, J., Coombs, G. H., Mottram, J. C. and Lima, A. P. C.A. (2008) The role of conserved residues of chagasin in the inhibition of cysteine peptidases. FEBS Letters, 582(4), pp. 485-490. (doi:10.1016/j.febslet.2008.01.008)

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Publisher's URL: http://dx.doi.org/10.1016/j.febslet.2008.01.008

Abstract

We have evaluated the roles of key amino acids to the action of the natural inhibitor chagasin of papain-family cysteine peptidases. A W93A substitution decreased inhibitor affinity for human cathepsin L 100-fold, while substitutions of T31 resulted in 10-100-fold increases in the Ki for cruzipain of Trypanosoma cruzi. A T31A/T32A double mutant had increased affinity for cathepsin L but not for cruzipain, while the T31-T32 deletion drastically affected inhibition of both human and parasite peptidases. These differential effects reflect the occurrence of direct interactions between chagasin and helix 8 of cathepsin L, interactions that do not occur with cruzipain

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Dr Brian and Mottram, Professor Jeremy
Authors: dos Reis, F. C.G., Smith, B. O., Santos, C. C., Costa, T., F., Scharfstein, J., Coombs, G. H., Mottram, J. C., and Lima, A. P. C.A.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:FEBS Letters
Publisher:Elsevier BV
ISSN:0014-5793
ISSN (Online):1873-3468
Published Online:15 January 2008
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
241291Molecular Genetic and Biochemical Analyses of ParasitesJeremy MottramMedical Research Council (MRC)G97222968Infection Immunity and Inflammation Life Sciences