Specificity of yeast KEX2 protease for variant human proalbumins is identical to the in vivo specificity of the hepatic proalbumin convertase.

摘要: Yeast KEX2 protease was examined as a potential model for human proprotein convertase and, in all respects, mimicked the predicted properties of proalbumin convertase. The enzyme rapidly cleaved propeptide Arg-Gly-Val-Phe-Arg-Arg from NH2-terminal end but, unlike trypsin, failed to cleave physiologically unprocessed variants. There little or no cleavage Lille (Arg-2----His) Christchurch (Arg-1----Gln), and there negligible Blenheim (Asp1----Val), despite fact that it retains dibasic processing signal. Proalbumin Kaikoura (Arg-2----Cys), which appears be partially processed vivo, at about half rate normal absence diarginyl sequence. Restoration site through aminoethylation new cysteine increased near proalbumin. KEX2-catalyzed found independent pH between 6.0 8.0. Antitrypsin Pittsburgh (Met358----Arg), specific inhibitor vivo cleavage, inhibited reversible manner. A molar excess thrombin over antitrypsin relieved inhibition KEX2, suggesting covalent complex is not formed inhibitor.