Characterization of the S3 Subsite Specificity of Cathepsin B
| Autor: | Isidoros Vlattas, Iou-Iou Sytwu, Tomoko Hirama, Regine Bohacek, Anna K. Knap, Carol P. Huber, Sadiq Hasnain, Harvey Kaplan, Alpay Taralp |
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| Rok vydání: | 1995 |
| Předmět: |
Models
Molecular musculoskeletal diseases Specificity constant Stereochemistry Molecular Sequence Data Tripeptide Biochemistry Cathepsin B Substrate Specificity Hydrolysis Coumarins Animals Amino Acid Sequence Enzyme kinetics Amino acid residue Molecular Biology Cathepsin Chemistry Substrate (chemistry) Cell Biology Hydrogen-Ion Concentration Rats Kinetics Thermodynamics Oligopeptides |
| Zdroj: | Journal of Biological Chemistry. 270:18036-18043 |
| ISSN: | 0021-9258 |
| Popis: | Five synthetic substrates containing different amino acid residues at the P3 position (acetyl-X-Arg-Arg-AMC, where X is Gly, Glu, Arg, Val, and Tyr and where AMC represents 7-amindo-4-methylcoumarin) were used to investigate the S3 subsite specificity of cathepsin B. At pH 6.0, the specificity constant, kcat/Km, for tripeptide substrate hydrolysis was observed to increase in the order GluGlyArgValTyr. Molecular modeling studies of substrates containing a P3 Glu, Arg, or Tyr covalently bound as the tetrahedral intermediate to the enzyme suggest that the specificity for a P3 Tyr is because of a favorable aromatic-aromatic interaction with Tyr75 on the enzyme as well as a possible H bond between the P3 Tyr hydroxyl and the side chain carboxyl of Asp69. |
| Databáze: | OpenAIRE |
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