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)

Proteinases are thought to be responsible for cartilage and bone erosion noted in chronic inflammatory conditions. Suramin [8-(3-benzamindo-4-meta-1-benzamindo)naphthalene-1,3,5-trisulfonic acid], 10(-5) and 10(-4) M, inhibited the release of a mouse macrophage-derived cartilage proteoglycan-degrading enzyme. At 10(-5) M it antagonized the activity of beta-glucuronidase and cathepsin D derived from the mouse macrophage, as well as similar enzymes secreted by rat macrophages in vivo. When cultured at 10(-4) M with rabbit knee cartilage, it antagonized the autolytic release of proteoglycan, indicating an inhibitory activity against a chondrocyte-derived neutral proteinase. After in vivo treatment at 10 mg/kg/day s.c., it was ineffective in preventing the cartilage and bone erosion noted in the adjuvant arthritic rat.
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PMID:Divergent effects of suramin on in vitro and in vivo assays of cartilage degradation. 634 39

In this study, the effect of pH on the conformation and the reactivity of the Escherichia coli Hsp70 molecular chaperone DnaK was investigated using spectroscopic and chemical assays. DnaK exhibits negligible binding of the hydrophobic dye 1-anilino-naphthalene-8-sulfonate (ANS) between pH 7 to 5.0, whereas appreciable binding occurs between pH 4.5 to 4.0. The binding of ANS to a protein is diagnostic of the presence of accessible ordered hydrophobic surfaces. Such hydrophobic surfaces are often displayed by partially folded protein intermediates such as molten globules. Nucleotide inhibits 70% of the ANS binding at pH 4.5 but none of the ANS binding at pH 4.0. Proteolysis of nucleotide-free DnaK at pH 4.5 with cathepsin D yields detectable fragments (masses > 20 kDa) of the C-terminal peptide-binding domain but none of the N-terminal ATPase domain, thus the ATPase domain is preferentially targeted for proteolysis. In contrast, proteolysis of nucleotide-free DnaK at pH 4.0 with cathepsin D cuts near the linker region, yielding both functional domains. Our interpretation of these data is that incubation of DnaK at pH 4.5 produces a partially unfolded form of the ATPase domain, in which secondary structure is mainly intact, but tertiary structure is reduced. Incubation of the protein at pH 4.0 produces an intermediate in which both functional domains have collapsed and possibly separated. Nucleotide inhibits the conformational change that occurs at pH 4.5 but not at 4.0.
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PMID:Characterization of two partially unfolded intermediates of the molecular chaperone DnaK at low pH. 1208 1

Singlet oxygen is a causal factor in light-induced skin photoaging and the cytotoxic process of tumor cells in photodynamic chemotherapy. To develop a better understanding of the functional consequences of protein modification by singlet oxygen, the effects of naphthalene endoperoxide on lysosomal protease, cathepsin, were examined. When the soluble fraction of normal human fetal skin fibroblast cells was treated with the endoperoxide, the activities of cysteine proteases, cathepsins B and L/S, were inhibited, but that of aspartate protease, cathepsin D/E, was not. The reduction of the endoperoxide-treated soluble fractions by treatment with dithiothreitol barely recovered the activities. Cathepsin B, purified from normal human liver, exhibited similar profiles to that in cytosol. These data suggest that singlet oxygen oxidatively modifies an amino acid residue essential for catalysis and consequently results in the irreversible inactivation of cysteine protease-type cathepsin.
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PMID:Specific inactivation of cysteine protease-type cathepsin by singlet oxygen generated from naphthalene endoperoxides. 1584 81