Conformational Changes and Inhibitor Binding at the Active Site of Elastase

Elastase is one of a class of serine proteinases (Hartley, 1960) which also includes trypsin, chymotrypsin-A and chymotrypsin-B, enzymes which all exhibit a common catalytic mechanism for the hydrolysis of peptide bonds in dietary protein, but which differ markedly in their specificity towards the amino acid residues forming those bonds. Elastase is synthesized in the acinar tissue of mammalian pancreas as an inactive zymogen, proelastase, which on entering the duodenum is activated by the tryptic cleavage of a single peptide bond, releasing a small activation peptide (Gertler and Birk, 1970) to yield the active enzyme, a single polypeptide chain of 240 amino acid residues containing four disulfide bridges (Shotton and Hartley, 1970).