Binding structure of elastase inhibitor scyptolin A
Ute Matern1, Christian Schleberger, Stjepan Jelakovic
1Institut für Biologie II, Mikrobiologie, Albert-Ludwigs-Universität, Schänzlestrasse 1, D-79104 Freiburg im Breisgau, Germany.
Abstract:
Natural bioactive compounds are of general interest to pharmaceutical research because they may be used as leads in drug development campaigns. Among them, scyptolin A and B from Scytonema hofmanni PCC 7110 are known to inhibit porcine pancreatic elastase, which in turn resembles the attractive drug target neutrophil elastase. The crystal structure of scyptolin A as bound to pancreatic elastase was solved at 2.8 A resolution. The inhibitor occupies the most prominent subsites S1 through S4 of the elastase and prevents a hydrolytic attack by covering the active center with its rigid ring structure. The observed binding structure may help to design potent elastase inhibitors.
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