Isolation and characterization of two new Lys49 PLA2s with heparin neutralizing properties from Bothrops moojeni snake venom.
Among the proteins and peptides already characterized in Bothrops moojeni venom, two novel phospholipases A(2) (PLA(2)) have been purified and fully sequenced by ESI-MS/MS techniques. Both of them belong to the enzymatically non-active Lys49 variants of PLA(2). They consist of 122 amino acids and share a characteristic sequence in their C-terminal region composed of clusters of basic amino acids known to interact with heparin. Thus, as already established, heparin can be used as an antidote to antagonize some myotoxic PLA(2)s from venoms of Bothrops genus. The two PLA(2) variants were shown to interact in vitro with unfractionated heparin (UFH) and low molecular weight heparin (LMWH), neutralizing their anticoagulant properties. Although the influences of PLA(2)s from snake venoms on the blood coagulation system are known, their use to antagonize the anticoagulant effect of heparin in vitro or in vivo has never been proposed. These finding recommend diagnostic and therapeutic applications, which are currently investigated.
Perchuc
Anna Maria
AM
DSM Nutritional Products AG Branch Pentapharm, Aesch (BL), Switzerland. annaperchuc@gmail.com
Menin
Laure
L
Favreau
Philippe
P
Bühler
Beatrice
B
Bulet
Philippe
P
Schöni
Reto
R
Wilmer
Marianne
M
Ernst
Beat
B
Stöcklin
Reto
R
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D017837:Bothrops / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003435:Crotalid Venoms / Q000737:chemistry* / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006494:Heparin Antagonists / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008239:Lysine / Q000737:chemistry; D010741:Phospholipases A / Q000737:chemistry* / Q000494:pharmacology; D020033:Protein Isoforms / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D003435:Crotalid Venoms; D006494:Heparin Antagonists; D020033:Protein Isoforms; D010741:Phospholipases A; D008239:Lysine