Structure-activity relationship in the urokinase hydrolysis of alpha-N-acetyl-L-lysine anilides
| Autor: | Dimiter D. Petkov, Nikolina Stambolieva, Evdokia Christova, Ivan Pojarlieff |
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| Rok vydání: | 1975 |
| Předmět: |
Binding Sites
Chemistry Stereochemistry Hydrolysis Lysine Substituent Substrate (chemistry) Biochemistry Urokinase-Type Plasminogen Activator chemistry.chemical_compound Kinetics Structure-Activity Relationship Aniline Reaction rate constant Tetrahedral carbonyl addition compound Endopeptidases Humans Anilides Enzyme kinetics Solubility |
| Zdroj: | European journal of biochemistry. 51(1) |
| ISSN: | 0014-2956 |
| Popis: | The absence of both nonproductive binding and substrate activation and also the good solubility of the substrates make the urokinase-catalysed hydrolysis of specific anilides a very suitable reaction for substrate structure-enzyme activity studies. Derivatives of alpha-N-acetyl-L-lysine anilide with high sigma minus-value substituents in the aniline ring were synthesized. Rate constants kappa-cat. and apparent Michaelis-Menten constants K-m (app.) are presented. From the substituent dependence of kappa-cat. and from the fact that kappa-cat. is 13 to 37 times smaller than the deacylation rate constant it is concluded that the rate-limiting step proceeds prior to deacylation. The catalytic rate constant kappa-cat. obeys a linear free-energy relationship of the Hammett type with Q equals +0.72. Two different mechanisms implied by the results obtained from the model reaction (specific base and general acid-base catalysed hydrolysis of N-acetylglycine anilides under extreme conditions) are proposed in order to account for this positive and low Q-value. In the first mechanism the breakdown of an enzyme tetrahedral intermediate is rate-limiting, while in the second one its formation controls the overall rate. The discrimination between the two mechanisms, however, could not be found. |
| Databáze: | OpenAIRE |
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