PDBsum entry 1okx

Hydrolase/hydrolase inhibitor

PDB id: 1okx

Contents

Protein chains

240 a.a. *

Ligands

1BO-ALA-THR-THR-LEU-SUJ-CNT-VAL ×2

Waters ×105

* Residue conservation analysis

References listed in PDB file

Key reference

• Title: Binding structure of elastase inhibitor scyptolin a.
• Authors: U.Matern, C.Schleberger, S.Jelakovic, J.Weckesser, G.E.Schulz.
• Ref.: Chem Biol, 2003, 10, 997. [DOI no: 10.1016/j.chembiol.2003.10.001]
• PubMed id: 14583266

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.

Figure 2.
Figure 2. Stereo Views of Scyptolin A Binding to Porcine Pancreatic Elastase(A) Ribbon plot of elastase with the initial (F[o]-F[c]) electron density map of scyptolin A at a contour level of 3 σ. The final model of scyptolin A is drawn into the density. The side chains of the catalytic triad of elastase are given for reference (pink).(B) Stereo view of scyptolin A bound to elastase represented by its molecular surface. The catalytic triad beneath the surface is shown; the putative nucleophilic attack of the serine is indicated by a dashed red line. The inhibitor with its rigid cyclic peptide structure sits snugly in the active center pocket.

The above figure is reprinted by permission from Cell Press: Chem Biol (2003, 10, 997-0) copyright 2003.