PMID- 20036682 OWN - NLM STAT- MEDLINE DCOM- 20100609 LR - 20161125 IS - 1879-3150 (Electronic) IS - 0041-0101 (Linking) VI - 55 IP - 6 DP - 2010 Jun 1 TI - Isolation and characterization of two new Lys49 PLA2s with heparin neutralizing properties from Bothrops moojeni snake venom. PG - 1080-92 LID - 10.1016/j.toxicon.2009.12.007 [doi] AB - 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. CI - Copyright 2009 Elsevier Ltd. All rights reserved. FAU - Perchuc, Anna Maria AU - Perchuc AM AD - DSM Nutritional Products AG Branch Pentapharm, Aesch (BL), Switzerland. annaperchuc@gmail.com FAU - Menin, Laure AU - Menin L FAU - Favreau, Philippe AU - Favreau P FAU - Buhler, Beatrice AU - Buhler B FAU - Bulet, Philippe AU - Bulet P FAU - Schoni, Reto AU - Schoni R FAU - Wilmer, Marianne AU - Wilmer M FAU - Ernst, Beat AU - Ernst B FAU - Stocklin, Reto AU - Stocklin R LA - eng PT - Journal Article DEP - 20091228 PL - England TA - Toxicon JT - Toxicon : official journal of the International Society on Toxinology JID - 1307333 RN - 0 (Crotalid Venoms) RN - 0 (Heparin Antagonists) RN - 0 (Protein Isoforms) RN - EC 3.1.1.32 (Phospholipases A) RN - K3Z4F929H6 (Lysine) SB - IM MH - Animals MH - Blood Coagulation/drug effects MH - Blood Coagulation Tests MH - Bothrops/*physiology MH - Cell Survival/drug effects MH - Cells, Cultured MH - Chromatography, Gel MH - Chromatography, High Pressure Liquid MH - Crotalid Venoms/*chemistry/pharmacology MH - Fibroblasts/drug effects/pathology MH - Heparin Antagonists/*chemistry/pharmacology MH - Humans MH - Lysine/chemistry MH - Phospholipases A/*chemistry/pharmacology MH - Protein Isoforms/chemistry MH - Spectrometry, Mass, Electrospray Ionization MH - Tandem Mass Spectrometry EDAT- 2009/12/29 06:00 MHDA- 2010/06/10 06:00 CRDT- 2009/12/29 06:00 PHST- 2009/08/10 00:00 [received] PHST- 2009/12/09 00:00 [revised] PHST- 2009/12/10 00:00 [accepted] PHST- 2009/12/29 06:00 [entrez] PHST- 2009/12/29 06:00 [pubmed] PHST- 2010/06/10 06:00 [medline] AID - S0041-0101(09)00576-5 [pii] AID - 10.1016/j.toxicon.2009.12.007 [doi] PST - ppublish SO - Toxicon. 2010 Jun 1;55(6):1080-92. doi: 10.1016/j.toxicon.2009.12.007. Epub 2009 Dec 28.