The Tick-Derived Anticoagulant Madanin Is Processed by Thrombin and Factor Xa

Abstract : The cysteine-less peptidic anticoagulants madanin-1 and madanin-2 from the bush tick Haemaphysalis longicornis are the founding members of the MEROPS inhibitor family I53. It has been previously suggested that madanins exert their functional activity by competing with physiological substrates for binding to the positively charged exosite I (fibrinogen-binding exosite) of a-thrombin. We hereby demonstrate that competitive inhibition of a-thrombin by madanin-1 or madanin-2 involves binding to the enzyme's active site. Moreover, the blood coagulation factors IIa and Xa are shown to hydrolyze both inhibitors at different, although partially overlapping cleavage sites. Finally, the three-dimensional structure of the complex formed between human a-thrombin and a proteolytic fragment of madanin-1, determined by X-ray crystallography, elucidates the molecular details of madanin-1 recognition and processing by the proteinase. Taken together, the current findings establish the mechanism of action of madanins, natural anticoagulants that behave as cleavable competitive inhibitors of thrombin.
Type de document :
Article dans une revue
PLoS ONE, Public Library of Science, 2013, 8 (8), pp.e71866. 〈10.1371/journal.pone.0071866〉
Liste complète des métadonnées

Littérature citée [44 références]  Voir  Masquer  Télécharger

https://hal.archives-ouvertes.fr/hal-01612075
Contributeur : Colette Orange <>
Soumis le : vendredi 6 octobre 2017 - 14:25:31
Dernière modification le : vendredi 6 octobre 2017 - 14:26:14
Document(s) archivé(s) le : lundi 8 janvier 2018 - 11:34:30

Fichier

Plos_One_Vol_8_pp.e71866-1-718...
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Citation

Ana Figueiredo, Daniele De Sanctis, Pedro José Barbosa Pereira. The Tick-Derived Anticoagulant Madanin Is Processed by Thrombin and Factor Xa. PLoS ONE, Public Library of Science, 2013, 8 (8), pp.e71866. 〈10.1371/journal.pone.0071866〉. 〈hal-01612075〉

Partager

Métriques

Consultations de la notice

43

Téléchargements de fichiers

21