Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was shown previously that human bronchial mucus contains an acid-stable proteinase inhibitor directed against trypsin and chymotrypsin, polymorphonuclear granulocyte elastase and cathepsin G. In addition to this well-characterized inhibitor, designated here as BSI-ATE (identical with the inhibitor HUSI-I from human seminal plasma or antileucoprotease), another acid-stable inhibitor BSI-E is present in the mucus which exerts inhibitory activity towards porcine pancreatic and human granulocytic elastase, but not against trypsin, chymotrypsin, or granulocytic cathepsin G. This elastase-specific inhibitor was isolated by affinity chromatography. Its molecular mass and its amino acid composition are very similar to those of BSI-TE. An immunological cross-reactivity between both inhibitor species was not observed. In the mucus of patients suffering from obstructive airway disease the elastase-specific inhibitor is not present in the free form but can be liberated by acidification.
 ...
PMID:An elastase-specific inhibitor from human bronchial mucus. Isolation and characterization. 691 99

Guamerin, a canonical serine protease inhibitor from Hirudo nipponia, was identified as an elastase-specific inhibitor and has potential application in various diseases caused by elevated elastase concentration. However, the application of guamerin is limited because it also shows inhibitory activity against other proteases. To improve the selectivity of guamerin as an elastase inhibitor, it is essential to understand the binding mode of the inhibitor to elastase and to other proteases. For this purpose, we determined the crystal structure of guamerin in complex with chymotrypsin at 2.5 A resolution. The binding mode of guamerin on elastase was explored from the model structure of guamerin/elastase. Guamerin binds to the hydrophobic pocket of the protease in a substrate-like manner using its binding loop. In order to improve the binding selectivity of guamerin to elastase, several residues in the binding loop were mutated and the inhibitory activities of the mutants against elastase and chymotrypsin were monitored. The substitution of the Met36 residue for Ala in the P1 site increased the inhibitory activity against elastase up to 14-fold, while the same mutant showed 7-fold decreased activity against chymotrypsin compared to the wild-type guamerin. Furthermore, the M36A guamerin mutant more effectively protected endothelial cells against cell damage caused by elastase than the wild-type guamerin.
 ...
PMID:The crystal structure of guamerin in complex with chymotrypsin and the development of an elastase-specific inhibitor. 1815 25