A secondary C1s interaction site on C1‐inhibitor is essential for formation of a stable enzyme‐inhibitor complex

Abstract

This paper examines the location of a secondary binding site for C1s on C1‐inhibitor (C1‐inh) which is required for the formation of SDS‐stable C1s‐C1‐inh complexes. We used a synthetic peptide (residues 448–459) corresponding to the distal hinge region of C1‐inh. This peptide binds to C1s and C1s preincubated with the peptide cleaves C1‐inh but does not form a stable C1s‐C1‐inh complex. Computer modelling of C1‐inh shows that residues Q452, Q453 and F455 are surface‐exposed and that the secondary binding site may also include residues H291 and F292 which are conserved in serpins.© 1997 Federation of European Biochemical Societies.