Substrate specificity of cerebral cathepsin D and high-Mr aspartic endopeptidase.
The specificity of action of bovine brain cortex cathepsin D (EC 3.4.23.5) and high-Mr aspartic endopeptidase (EC 3.4.23.-) was studied with the vasoactive peptides renin substrate tetradecapeptide (RSTP), substance P (SP), and angiotensins I and II, and with model peptides--Lys-Pro-Ala-Glu-Phe-Phe (NO2)-Ala-Leu (I), Gly-Gly-His-Phe (NO2)-Phe-Ala-Leu-NH2 (II), and Abz-Ala-Ala-Phe-Phe-pNA (III). Cerebral aspartic peptidases show identical substrate specificity, cleaving the Leu10-Leu bond in RSTP and Phe-Phe in SP and peptide I-III, and not splitting angiotensins I and II. Because of the higher catalytic efficiency of cathepsin D (Kcat value), the specificity constants (Kcat/Km) for cathepsin D-catalyzed hydrolysis of substrates 1-111 are much higher than those for the high-Mr enzyme. High-Mr aspartic peptidase shares a number of properties with cathepsin D (sensitivity to pepstatin, substrate specificity, pH activity profile) and shows partial immunological identity; however, high-Mr aspartic peptidase has a specific activity 7-10 times lower than that of cathepsin D. The kinetic parameters of proteolysis of model peptides presented indicate that the high-Mr enzyme may be a complex of a single-chain cathepsin D with another polypeptide, although the possibility that it is an independent aspartic peptidase cannot be excluded.
Azaryan
A V
AV
Institute of Biochemistry, Yerevan, Union of Soviet Socialist Republics.
Galoyan
A A
AA
D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002402:Cathepsin D / Q000302:isolation & purification / Q000378:metabolism*; D002417:Cattle; D002540:Cerebral Cortex / Q000201:enzymology*; D010450:Endopeptidases / Q000378:metabolism*; D007700:Kinetics; D009479:Neuropeptides / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013379:Substrate Specificity
D009479:Neuropeptides; D010455:Peptides; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; D002402:Cathepsin D