The crystal structure of PR3, a neutrophil serine proteinase antigen of Wegener's granulomatosis antibodies.

摘要: The crystal structure of PR3, a serine proteinase from the azurophilic granules human polymorphonuclear neutrophils, has been solved by molecular replacement using leukocyte elastase structure. PR3 refined to an R-factor (= sigma parallel Fo magnitude of-Fc parallel/sigma Fo) 0.201 for all data in range 10.0 2.2 A resolution. enzyme was crystallized space group P21 with four molecules asymmetric unit (Vm approximately equal 2.6 A/Da). overall fold consists two domains beta-barrel structures typical chymotrypsin family proteinases. In general, substrate binding sites, S4 S3', are more polar than comparable sites related proteinase, elastase. experimentally observed preference small aliphatic residues at P1 position is explained Val Ile substitution 190 when compared Ala Asp 213 back S1 should not affect its specificity greatly, as side-chain points into interior protein. includes disaccharide (N-linked 2-acetamido-2-deoxy-beta-D-glucopyranose and 1,6-linked alpha-L-fucopyranose) covalently attached Asn 159. linear antigenic reported react Wegener's granulomatosis autoantibodies occur regions three-dimensional that may implicate inactive pro-form pathogenesis disease.