Human neutrophil proteinase 3: mapping of the substrate binding site using peptidyl thiobenzyl esters

Abstract

A series of peptidyl thiobenzyl esters was used to map the active site of human leukocyte proteinase 3. The steady-state kinetics parameters reveal the following features regarding the substrate specificity of proteinase 3 and its putative active site: (a) the preferred P1 residue is a small hydrophobic amino acid such as aminobutyric acid, norvaline, valine or alanine (in decreasing order of preference); (b) the enzyme has an extended active site; and (c) its active site is similar to that of the related serine proteinases leukocyte elastase and leukocyte cathepsin G.