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

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

doi:https://doi.org/10.1016/S1570-9639(04)00051-2

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

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

Research output: Contribution to journal › Article › Academic › peer-review

3 Citations (Scopus)

Abstract

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

Original language	English
Pages (from-to)	139-144
Journal	BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
Volume	1699
Issue number	1-2
DOIs	https://doi.org/10.1016/S1570-9639(04)00051-2
Publication status	Published - 2004

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https://doi.org/10.1016/S1570-9639(04)00051-2

Cite this

@article{a69155b597c34774b42afed42d6dac3d,

title = "Effect of reactive site loop elongation on the inhibitory activity of C1-inhibitor",

abstract = "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",

author = "Bos, {I. G. A.} and Lubbers, {Y. T. P.} and E. Eldering and Abrahams, {J. P.} and Hack, {C. E.}",

year = "2004",

doi = "https://doi.org/10.1016/S1570-9639(04)00051-2",

language = "English",

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journal = "BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS",

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T1 - Effect of reactive site loop elongation on the inhibitory activity of C1-inhibitor

AU - Bos, I. G. A.

AU - Lubbers, Y. T. P.

AU - Eldering, E.

AU - Abrahams, J. P.

AU - Hack, C. E.

PY - 2004

Y1 - 2004

N2 - 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

AB - 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

U2 - https://doi.org/10.1016/S1570-9639(04)00051-2

DO - https://doi.org/10.1016/S1570-9639(04)00051-2

M3 - Article

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SN - 1570-9639

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JO - BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

JF - BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

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