Proteinases as Drug Targets
Chapter 10: Structural Mechanisms of Inactivation in Proteolytically Inactive Serine Proteases from Sarcoptes scabiei
Published:22 Nov 2011
The scabies mite (Sarcoptes scabiei) is a parasitic mite responsible for major morbidity in disadvantaged communities and immuno-compromised patients worldwide. The scabies mite produces 33 proteins that are closely related to the dust mite group 3 allergen and belong to the S1-like protease family (chymotrypsin-like). However, all but one of these molecules contain mutations in the conserved active-site catalytic triad that are predicted to render them catalytically inactive. These molecules are thus termed Scabies Mite Inactivated Protease Paralogues (SMIPPs). The precise function of SMIPPs remains unclear. However, it has been suggested that these proteins may function by binding and protecting target substrates from cleavage by host immune proteases, thus preventing the host from mounting an effective immune challenge. The high-resolution crystal structures of two members of the SMIPP family have been solved and provide insight into how SMIPPs have lost the ability to bind substrates in a classical ‘canonical’ fashion, and instead have evolved alternative functions in the lifecycle of the Scabies mite.