Alkaline serine protease produced by Streptomyces sp. degrades PrPSc

• DOI: 10.1016/j.bbrc.2004.06.100
• Publication Date: 2004-07-07T11:49:56Z
• Authors: Zhao Hui; Hiroyasu Doi; Hiroaki Kanouchi; Yuichi Matsuura; Shiro Mohri; Yoshiaki Nonomura; Tatsuzo Oka
• Keywords: 0301 basic medicine; PrPSc Proteins; Molecular Sequence Data; Serine Endopeptidases; Brain; Peptide Fragments; Streptomyces; Kinetics; 03 medical and health sciences; Bacterial Proteins; Cricetinae; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Animals; Trypsin; Amino Acid Sequence

A PrP(Sc)-degrading enzyme was isolated from the culture medium of Streptomyces sp. using perchloric acid-soluble protein (PSP) as a substrate. The media of 500 microbial species were screened to obtain the PSP-degrading enzyme. The medium containing the protease secreted from strain 99-GP-2D-5 showed the highest PSP-degrading activity. Strain 99-GP-2D-5 was assigned as the genus Streptomyces by its morphological and chemotaxonomic characteristics. When scrapie prion was used as the substrate, it was completely digested by the enzyme. The amino acid sequence of the enzyme was identical to that of the C-terminal region of alkaline serine protease (ASP) I. ASP I may be the precursor of the enzyme, and the enzyme seems to be the mature type of ASP I. The maximal activity of the enzyme was observed at 60 degrees C and pH 11, and the scrapie prion was degraded within 3 min under the optimum conditions.