By a News Reporter-Staff News Editor at Biotech Week -- Researchers detail new data in Enzymes and Coenzymes. According to news reporting out of Victoria, Australia, by NewsRx editors, research stated, "The serine protease, C1r, initiates activation of the classical pathway of complement, which is a crucial innate defense mechanism against pathogens and altered-self cells. C1r both autoactivates and subsequently cleaves and activates C1s."
Our news journalists obtained a quote from the research from Monash University, "Because complement is implicated in many inflammatory diseases, an understanding of the interaction between C1r and its target substrates is required for the design of effective inhibitors of complement activation. Examination of the active site specificity of C1r using phage library technology revealed clear specificity for Gln at P2 and Ile at P1', which are found in these positions in physiological substrates of C1r. Removal of one or both of the Gln at P2 and Ile at P1' in the C1s substrate reduced the rate of C1r activation. Substituting a Gln residue into the P2 of the activation site of MASP-3, a protein with similar domain structure to C1s that is not normally cleaved by C1r, enabled efficient activation of this enzyme. Molecular dynamics simulations and structural modeling of the interaction of the C1s activation peptide with the active site of C1r revealed the molecular mechanisms that particularly underpin the specificity of the enzyme for the P2 Gln residue. The complement control protein domains of C1r also made important contributions to efficient activation of C1s by this enzyme, indicating that exosite interactions were also important."
According to the news editors, the research concluded: "These data show that C1r specificity is well suited to its cleavage targets and that efficient cleavage of C1s is achieved through both active site and exosite contributions."
For more information on this research see: Molecular determinants of the substrate specificity of the complement-initiating protease, C1r. Journal of Biological Chemistry, 2013;288(22):15571-80. (American Society for Biochemistry and Molecular Biology - www.asbmb.org; Journal of Biological Chemistry - www.jbc.org/)
Our news journalists report that additional information may be obtained by contacting L.C. Wijeyewickrema, Dept. of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. Additional authors for this research include T. Yongqing, T.P. Tran, P.E. Thompson, J.E. Viljoen, T.H. Coetzer, R.C. Duncan, I. Kass, A.M. Buckle and R.N Pike (see also Enzymes and Coenzymes).
Keywords for this news article include: Biotechnology, Victoria, Genetics, Genomics, Protease, Proteomics, Phage Libraries, Enzymes and Coenzymes, Australia and New Zealand.
Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2013, NewsRx LLC