Primary structure of the reactive site of human C1-inhibitor.
Human C1-inhibitor (C1-Inh) forms an equimolar complex with complement proteinase C1s that is resistant to dissociation by sodium dodecyl sulfate. The formation of this stable complex results in the cleavage of a peptide bond near the carboxyl terminus of the inhibitor and, whereas the bulk of C1-Inh remains covalently bound to the light chain of C1s, the postcomplex inhibitor peptide can be isolated under denaturing conditions. We have sequenced the amino-terminal region of this peptide and deduced that it represents the carboxyl-terminal side of the reactive site of C1-Inh. Limited proteolysis of C1-Inh by Crotalus atrox protease results in an active derivative lacking an amino-terminal peptide of 36 residues. Further proteolysis of this derivative with Pseudomonas aeruginosa elastase inactivates the inhibitor and a peptide is released. The amino-terminal sequence of this peptide overlaps with that of the postcomplex peptide and indicates that the residue imparting primary specificity to the inhibitor is arginine.
D000595:Amino Acid Sequence; D001665:Binding Sites; D003166:Complement Activating Enzymes / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D003173:Complement C1s; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D008666:Metalloendopeptidases; D008970:Molecular Weight; D010196:Pancreatic Elastase / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000201:enzymology
D003174:Complement C1 Inactivator Proteins; D007531:Isoflurophate; D003166:Complement Activating Enzymes; D010450:Endopeptidases; D010196:Pancreatic Elastase; D003173:Complement C1s; D008666:Metalloendopeptidases; C044577:atrolysin A