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