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Professor David J Kemp

Queensland Institute of Medical Research
Brisbane, Qld 4006
Email: daveK@qimr.edu.au
Tel: +61-7-3362 0402
Fax: +61-7-3362 0104
Homepage: http://www.qimr.edu.au/research/labs/davek/

We have unexpectedly discovered two multigene families in the scabies mite Sarcoptes scabiei which encode genetically inactivated proteases. In an EST library we identified 24 distinct contigs with the serine protease group 3 house dust mite allergen as their closest homologue. Remarkably in all but one of these the active serine, histidine and/or aspartic acid was mutated. Hence these genes are no longer a family of active proteases. Phylogenetic relationships suggested that inactivation occurred prior to successive gene duplications.
We also identified a multigene family of S. scabiei homologues of the house dust mite group 1 allergen, a cysteine protease. Five of these encode putatively active proteases while the other five encode molecules with both the essential cysteine and histidine of the active site mutated and thus cannot function as active proteases by any known mechanism. They have been termed the Scabies Mite Inactived Protease Paralogue (SMIPP) families.
We hypothesised that SMIPPs may mediate competitive inhibition of proteases of the blood coagulation cascade, or mechanisms such as antagonisation of cleavage of protease activated receptors to diminish inflammation. While the interactions of SMIPPs with host mechanisms remain to be elucidated, the similarities in evolution of these unprecedented families emphasises their importance. We wish to examine the ability of SMIPPs to bind to peptides and to act as competitive inhibitors for proteases that have a variety of biological activities. These molecules may well provide novel targets for clinical intervention.
Dr. Deborah Holt, QLD Institute of Medical Research
Dr. Katja Fischer, QLD Institute of Medical Research
Dr. Shelley Walton, Menzies School of Health Research
Dr. Rob Pike, Monash University
Dr David Fairlie, University of Queensland
Dr. Nick Hoogenraad, Latrobe University
Holt et al, mechanisms for a novel immune evasion strategy in the scabies mite Sarcoptes scabiei. J.Invest Dermatol 2003, 121, 1419-1424

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