Structure and function of C1-inhibitor.
C1-INH belongs to the family of serpins. Structural studies have yielded a clear understanding of the biochemical principle underlying the functional activities of these proteins. Although the crystal structure of C1-INH has yet to be revealed, homology modeling has provided a three-dimensional model of the serpin part of C1-INH. This model has helped us understand the biochemical consequences of mutations of the C1-INH gene as they occur in patients who have HAE. The structure of the N-terminal domain of C1-INH remains unknown; however, this part of the molecule is unlikely to be important in the inhibitory activity of C1-INH toward its target proteases. Mutations in this part have not been described in patients who have HAE, except for a deletion containing two cysteine residues involved in the stabilization of the serpin domain. Recent studies suggest some anti-inflammatory functions for this N-terminal part, possibly explaining the effects of C1-INH in diseases other than HAE.
Wagenaar-Bos
Ineke G A
IG
Department of Immunopathology, Sanquin Research at CLB and Landsteiner Laboratory, Academical Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands. i.bos@sanquin.nl
Hack
C Erik
CE
D000595:Amino Acid Sequence; D050718:Complement C1 Inhibitor Protein / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship
D050718:Complement C1 Inhibitor Protein