Acidic pH as a physiological regulator of human cathepsin L activity
| Autor: | B, Turk, I, Dolenc, B, Lenarcic, I, Krizaj, V, Turk, J G, Bieth, I, Björk |
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| Rok vydání: | 1999 |
| Předmět: |
Protein Denaturation
Cathepsin L Circular Dichroism Molecular Sequence Data Molecular Conformation Temperature Hydrogen-Ion Concentration Cathepsin D Cathepsins Protein Structure Secondary Cysteine Endopeptidases Kinetics Endopeptidases Enzyme Stability Solvents Humans Dimethyl Sulfoxide Amino Acid Sequence Lysosomes |
| Zdroj: | European journal of biochemistry. 259(3) |
| ISSN: | 0014-2956 |
| Popis: | Human cysteine protease cathepsin L was inactivated at acid pH by a first-order process. The inactivation rate decreased with increasing concentrations of a small synthetic substrate, suggesting that substrates stabilize the active conformation. The substrate-independent inactivation rate constant increased with organic solvent content of the buffer, consistent with internal hydrophobic interactions, disrupted by the organic solvent, also stabilizing the enzyme. Circular dichroism showed that the inactivation is accompanied by large structural changes, a decrease in alpha-helix content being especially pronounced. The high activation energy of the reaction at pH 3.0 (200 kJ.mol-1) supported such a major conformational change occurring. The acid inactivation of cathepsin L was irreversible, consistent with the propeptide being needed for proper folding of the enzyme. Aspartic protease cathepsin D was shown to cleave denatured, but not active cathepsin L, suggesting a potential mechanism for in-vivo regulation and turnover of cathepsin L inside lysosomes. |
| Databáze: | OpenAIRE |
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