Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 20% of the radioactivity incorporated into the dentine collagen of unerupted bovine molars after reduction with tritiated sodium borohydride was recovered in a cyanogen bromide peptide fraction of Mr 61 000 following chromatography on agarose A5m. After rechromatography on agarose A1.5m, this fraction was resolved into ten components by gel isoelectric focusing. Of these components, nine (the most acidic) were tritiated and contained the reduced cross-links dihydroxylysinonorleucine and hydroxylysinonorleucine. The amino acid compositions were consistent with the identification of each of these components as alpha 2CB3,5 linked to one or two small peptides. By limited Edman degradation, with and without prior digestion with pyroglutamate aminopeptidase (EC 3.4.11.8), these small peptides were identified as alpha 1CB0,1 and alpha 2CB1, occurring in a ratio of approximately 2:1. Specific cleavage with cathepsin D revealed that all the cross-link was associated with the C-terminal one-third of the alpha 2 chain, thus fixing the displacement of the participating molecules at 4D. The content of the known reducible cross-links present in these peptides, calculated from the specific activity of the reductant, was sufficient to account for only 10--20% of the cross-linking actually found, suggesting that stabilization is mainly through nonreducible cross-links of as yet undetermined structure. By quantitative analysis of homoserine content and semiquantitative amino-terminal analyses, it was determined that virtually all of the alpha 2 chain of bovine dentine collagen is cross-linked in this manner. One cross-link per molecule in this location could made a major contribution to the mechanical stability of the insoluble collagen fibrils in this tissue.
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PMID:A major intermolecular cross-linking site in bovine dentine collagen involving the alpha 2 chain and stabilizing the 4D overlap. 747 Apr 54