Expression and substrate specificity of a recombinant cysteine proteinase B of Leishmania braziliensis

Lanfranco, M. F. et al. (2008) Expression and substrate specificity of a recombinant cysteine proteinase B of Leishmania braziliensis. Molecular and Biochemical Parasitology, 161(2), pp. 91-100. (doi:10.1016/j.molbiopara.2008.06.005)

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Publisher's URL: http://dx.doi.org/10.1016/j.molbiopara.2008.06.005

Abstract

The cysteine proteinase B of Leishmania parasites is an important virulence factor. In this study we have expressed, isolated and characterized for the first time a recombinant CPB from Leishmania braziliensis, the causative agent of mucocutaneous leishmaniosis. The mature region of the recombinant CPB shares a high percentage identity with its Leishmania mexicana CPB2.8 (rCPB2.8 Delta CTE) counterpart (76.36%) and has identical amino acid residues at the S-1, catalytic triad and S'(1) subsites. Nevertheless, when the kinetics of substrate hydrolysis was measured using a combinatorial library of internally quenched fluorescent peptides based upon the lead sequence Abz-KLRSSKQ-EDDnp, significant differences were obtained. These results suggest that the differences in substrate utilization observed between the L. mexicana and L. braziliensis CPs must be related to amino acid modifications outside the core of the active site cleft. Moreover, a potent inhibitor with Pro at P1 and high affinity for L. braziliensis recombinant CPB showed less affinity to L. mexicana CPB 2.8, which preferred Phe, Leu, and Asn at the same position.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mottram, Professor Jeremy and Coombs, Professor Graham
Authors: Lanfranco, M. F., Loayza-Muro, R., Clark, D., Nunez, R., Zavaleta, A. I., Jimenez, M., Meldal, M., Coombs, G. H., Mottram, J. C., Izidoro, M., Juliano, M. A., Juliano, L., and Arevalo, J.
Subjects:Q Science > QL Zoology
Q Science > QH Natural history > QH301 Biology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Molecular and Biochemical Parasitology
Publisher:Elsevier BV
ISSN:0166-6851
ISSN (Online):1872-9428
Published Online:20 June 2008
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
297261Post-genomic analysis of cysteine protease function in Leishmania parasitesJeremy MottramMedical Research Council (MRC)G0000508Infection Immunity and Inflammation Life Sciences