Effect of reactive site loop elongation on the inhibitory activity of C1-inhibitor

Bos, I.G.A.; Lubbers, Y.T.P.; Eldering, E.; Abrahams, J.P.; Hack, C.E. (2004)

Article / Letter to editor

The serine protease inhibitor C1-Inhibitor (C1-Inh) inhibits several complement- and contact-system proteases, which play an important role in inflammation. C1-Inh has a short reactive site loop (RSL) compared to other serpins. RSL length determines the inhibitory activity of serpins. We investigated the effect of RSL elongation on inhibitory activity of C1-Inh by insertion of one or two alanine residues in the RSL. One of five mutants had an increased association rate with kallikrein, but was nevertheless a poor inhibitor because of a simultaneous high stoichiometry of inhibition (>10). The association rate of the other variants was lower than that of wild-type C1-Inh. These data suggest that the relatively weak inhibitory activity of C1-Inh is not the result of its short RSL. The short RSL of C1-Inh has, surprisingly, the optimal length for inhibition. (C) 2004 Elsevier B.V. All rights reserved.

• All authors: Bos, I.G.A.; Lubbers, Y.T.P.; Eldering, E.; Abrahams, J.P.; Hack, C.E.
• Date: 2004-06-01
• Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
• Volume: 1699
• Issue: 1-2
• Pages: 139 - 144
• DOI: doi:10.1016/j.bbapap.2004.02.006