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ON THE SEQUENTIAL CLEAVAGE OF MYELIN BASIC PROTEIN BY CATHEPSINS A AND D
Author(s) -
Marks N.,
Grynbaum A.,
Benuck M.
Publication year - 1976
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1976.tb10405.x
Subject(s) - cathepsin a , myelin basic protein , cathepsin o , biochemistry , carboxypeptidase , cathepsin , aminopeptidase , cleavage (geology) , cathepsin d , cathepsin c , chemistry , cathepsin l1 , enzyme , cathepsin h , exopeptidase , tripeptide , myelin , biology , amino acid , leucine , central nervous system , endocrinology , paleontology , fracture (geology)
— A lysosomal carboxypeptidase (cathepsin A) known to increase in demyelination (experimental allergic encephalomyelitis and multiple sclerosis) and purified 277 fold from bovine brain failed to attack myelin basic protein. Prior treatment of basic protein with bovine cathepsin D (EC 3.4.23.5) at pH 3.2 led to the production of three polypeptides one of which, Phe 43 ‐Phe 88 , acted as a substrate for the carboxypeptidase. Incubation of this fragment with cathepsin A at pH 5.5 led to the release of C‐terminal Phe equivalent to 50% of the total within 6h at 25°C and smaller amounts of the adjacent His (position 87) and Val (86). Purified cathepsin A was devoid of aminopeptidase and arylamidase contaminants when tested with a variety of di‐ and tripeptides and with the polypeptide fragment of myelin basic protein Phe 89 ‐Arg 169 . These studies in vitro with two different lysosomal enzymes show that cathepsin D activity is rate‐limiting. A demonstration of step‐wise cleavage by lysosomal enzymes may be relevant to mechanisms regulating protein turnover and to processes involved in demyelination.