Differences in transition state stabilization between thermolysin (EC 3.4.24.27) and neprilysin (EC 3.4.24.11). - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue FEBS Letters Année : 1998

Differences in transition state stabilization between thermolysin (EC 3.4.24.27) and neprilysin (EC 3.4.24.11).

Résumé

Important homologies in the topology of the catalytic site and the mechanism of action of thermolysin and neprilysin have been evidenced by site-directed mutagenesis. The determination of differences in transition state stabilization between these peptidases could facilitate the design of specific inhibitors. Thus, two residues of thermolysin which could be directly (Tyr157) or indirectly (Asp226) involved in the stabilization of the transition state and their putative counterparts in neprilysin (Tyr625 and Asp709) have been mutated. The results show that Tyr157 is important for thermolysin activity while Tyr625 has no functional role in neprilysin. Conversely, the mutation of Asp226 induced a slight perturbation of thermolysin activity while Asp709 in neprilysin seems crucial in neprilysin catalysis. Taken together these data seem to indicate differences in the transition state mode of stabilization in the two peptidases.
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Dates et versions

inserm-00145191 , version 1 (09-05-2007)

Identifiants

  • HAL Id : inserm-00145191 , version 1
  • PUBMED : 9827548

Citer

Cynthia Marie-Claire, Emmanuel Ruffet, Gilles Tiraboschi, Marie-Claude Fournie-Zaluski. Differences in transition state stabilization between thermolysin (EC 3.4.24.27) and neprilysin (EC 3.4.24.11).. FEBS Letters, 1998, 438 (3), pp.215-9. ⟨inserm-00145191⟩
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