Stabilization of porcine pancreatic elastase crystals by glutaraldehyde cross-linking

摘要

Elastase is a serine protease from the chymotrypsin family of enzymes with the ability to degrade elastin, an important component of connective tissues. Excessive elastin proteolysis leads to a number of pathological diseases. Porcine pancreatic elastase (PPE) is often used for drug development as a model for human leukocyte elastase (HLE), with which it shares high sequence identity. Crystals of PPE were grown overnight using sodium sulfate and sodium acetate at acidic pH. Cross-linking the crystals with glutaraldehyde was needed to resist the soaking procedure with a diethyl N-(methyl) pyridinyl-substituted oxo-beta-lactam inhibitor. Crystals of PPE bound to the inhibitor belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 51.0, b = 58.3, c = 74.9 angstrom, and diffracted to 1.8 angstrom resolution using an in-house X-ray source.