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.
Perani
P
P
Vieillissement et Pathologie de la Retine, INSERM, Unité U450 Developpement, 29, rue Wilhem, Paris, 75016, France. perani@infobiogen.fr
Zeggai
S
S
Torriglia
A
A
Courtois
Y
Y
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