The X-ray Crystal Structure of Mannose-Binding Lectin-Associated Serine Proteinase-3
News Jun 27, 2013
The mannose-binding lectin associatedprotease-3 (MASP-3) is a member of the lectin pathway of the complement system, a key component of human innate and active immunity. Mutations in MASP-3 have recently been found to be associated with Carnevale, Mingarelli, Malpuech and Michels (3MC) syndrome, a severe developmental disorder manifested by cleft palate, intellectual disability and skeletal abnormalities. However, the molecular basis for MASP-3 function remains to be understood. Here we characterise the substrate specificity of MASP-3 by screening against a combinatorial peptide substrate library. Through this approach, we successfully identified a peptide substrate that was 20-fold more efficiently cleaved than any other identified to date. Further, we demonstrated that mutant forms of the enzyme associated with 3MC syndrome were completely inactive against this substrate. To address the structural basis for this defect, we determined the 2.6 Å structure of the zymogen form of the G666E mutant of MASP-3. These data reveal that the mutation disrupts the active site and perturbs the position of the catalytic serine residue. Together, these insights into the function of MASP-3 reveal how a mutation in this enzyme causes it to be inactive and thus contribute to the 3MC syndrome.
This article was published online in The Journal of Biological Chemistry and is free to access.
Elpis BioMed Closes Funding Round to Commercialise Novel Technology Platform for Generating Human Cell TypesNews
New Cambridge spin-out company commercialises disruptive technology that enables rapid generation of pure and consistent batches of human cell types. Geographically diversified, top-tier investor team includes key industry leaders to support early company development.READ MORE
Quotient Sciences Acquires Pharmaterials, a UK-based Contract Development and Manufacturing OrganizationNews
Quotient Sciences, the drug development services organization, announces it has acquired Pharmaterials, a contract development and manufacturing organization (CDMO) based in Reading, U.K..READ MORE
BOC Sciences Continues to Enlarge Its Publication Collection Using BOC Sciences ProductsNews
BOC Sciences continues to add more publication items that used BOC Sciences products in their researches to its already existing collection.READ MORE