Cooperative effects in the substrate specificity of the complement protease C1s.
Complement is a key component of the immune system, but can contribute to inflammatory diseases. The substrate specificity of C1s protease has been successfully investigated using a combinatorial approach, while a positional scanning method failed. The lack of success of the latter approach is possibly due to cooperativity in the active site, which could confound such analyses. With a panel of peptides devised using factorial design, we show pronounced cooperativity between the S4 and S1' subsites in the active site of the enzyme, and weaker cooperativity between the S1' and S3' subsites. The use of factorial design has promise as a methodology for determining cooperativity in protease active sites.
Clayton School of Information Technology, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
Sarah E
SE
Boyd
Felicity K
FK
Kerr
David W
DW
Albrecht
Maria Garcia
MG
de la Banda
Natasha
N
Ng
Robert N
RN
Pike
D001665:Binding Sites; D020134:Catalytic Domain; D003173:Complement C1s / Q000737:chemistry* / Q000378:metabolism*; D005163:Factor Analysis, Statistical; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D012107:Research Design; D013379:Substrate Specificity
D019151:Peptide Library; D010455:Peptides; D003173:Complement C1s