Binding structure of elastase inhibitor scyptolin A.
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.
Institut für Biologie II, Mikrobiologie, Albert-Ludwigs-Universität, Schänzlestrasse 1, D-79104 Freiburg im Breisgau, Germany.
Ute
U
Matern
Christian
C
Schleberger
Stjepan
S
Jelakovic
Jürgen
J
Weckesser
Georg E
GE
Schulz
D001665:Binding Sites; D018360:Crystallography, X-Ray; D000458:Cyanobacteria / Q000737:chemistry / Q000378:metabolism*; D047630:Depsipeptides; D004791:Enzyme Inhibitors / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000737:chemistry
D047630:Depsipeptides; D004791:Enzyme Inhibitors; D010456:Peptides, Cyclic; C448645:scyptolin A; D010196:Pancreatic Elastase; D014357:Trypsin