Novel catalytically-inactive PII metalloproteinases from a viperid snake venom with substitutions in the canonical zinc-binding motif
Fecha
2016-10-12
Tipo
artículo original
Autores
Camacho Umaña, Erika
Sanz, Libia
Escalante Muñoz, Teresa
Pérez, Alicia
Villalta Romero, Fabián
Lomonte, Bruno
Neves Ferreira, Ana Gisele da Costa
Feoli Grant, Andrés
Calvete Chornet, Juan José
Gutiérrez, José María
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Resumen
Snake venom metalloproteinases (SVMPs) play key biological roles in prey immobilization
and digestion. The majority of these activities depend on the hydrolysis of relevant protein substrates
in the tissues. Hereby, we describe several isoforms and a cDNA clone sequence, corresponding to PII
SVMP homologues from the venom of the Central American pit viper Bothriechis lateralis, which have
modifications in the residues of the canonical sequence of the zinc-binding motif HEXXHXXGXXH.
As a consequence, the proteolytic activity of the isolated proteins was undetectable when tested on
azocasein and gelatin. These PII isoforms comprise metalloproteinase and disintegrin domains
in the mature protein, thus belonging to the subclass PIIb of SVMPs. PII SVMP homologues
were devoid of hemorrhagic and in vitro coagulant activities, effects attributed to the enzymatic
activity of SVMPs, but induced a mild edema. One of the isoforms presents the characteristic RGD
sequence in the disintegrin domain and inhibits ADP- and collagen-induced platelet aggregation.
Catalytically-inactive SVMP homologues may have been hitherto missed in the characterization of
snake venoms. The presence of such enzymatically-inactive homologues in snake venoms and their
possible toxic and adaptive roles deserve further investigation.
Descripción
Palabras clave
Snake venom metalloproteinases, PII SVMP homologues, Disintegrin domain, Zinc-binding motif, Hemorrhagic activity, Platelet aggregation, Proteinase activity, Proteinase, Snake venom