Mutations on the hinge region of leukocyte elastase inhibitor determine the loss of inhibitory function.
Leukocyte elastase inhibitor (LEI) is a cytosolic component of lung macrophages and blood leukocytes that inhibits neutrophil elastase. LEI is a member of the serpin superfamily, these proteins, mostly protease inhibitors, are thought to undergo a conformational change upon complex formation with proteinase that involves partial insertion of the hinge region of the reactive centre loop into a beta-sheet of the inhibitor. In this work three mutations were produced in the hinge region of elastase inhibitor that abolish the inhibition activity of LEI and transform the protein in a substrate of the elastase. This result demonstrates that the inhibitory mechanism of serpin is common to LEI.
Vieillissement et Pathologie de la Retine, INSERM, Unité U450 Developpement, 29, rue Wilhem, Paris, 75016, France. perani@infobiogen.fr
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Perani
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Zeggai
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Torriglia
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Courtois
D000595:Amino Acid Sequence; D000818:Animals; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D015843:Serpins / Q000235:genetics* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D015843:Serpins