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Snake Venom and Haemostasis – An Overview
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28092–7. angiogenesis, Angiogenesis, 1999;3:259–69. activates platelets by a mechanism involving glycoprotein VI as
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Related Articles
Molecular Cloning and Sequence Analysis of Catalytically Inactive Phospholipase A
2
Homologue
Alboaggregin B Binds to Vascular Endothelial Growth Factor
Arpijuntarangkoon J, et al. Receptor-2 via a C-terminal Loop Region
Platelets, 2007;18(4):266–72. Fujisawa D, et al.
Biochem J, 2008;411(3):515–22.
Green pit viper (Trimeresurus albolabris) venom contains a variety of
C-type lectin-like proteins (CLPs) causing platelet aggregation and Vascular endothelial growth factor (VEGF) regulates neovascularisation
consumptive thrombocytopenia in biting victims. Alboaggregin B through binding to its receptor kinase insert domain-containing
(AL-B), a heterodimeric glycoprotein (Gp) Ib-binding protein, was receptor (KDF; VEGF receptor-2). The authors identified a catalytically
purified from the venom, but there is no reported complementary DNA inactive PLA
2
(phospholipase A
2
) homologue (KDR-bp) in the venom
(cDNA) sequence and the platelet agglutination mechanism is poorly of eastern cottonmouth (Agkistrodon piscivorus piscivorus) as a third
understood. The full-length AL-B beta clone was obtained from the KDR-binding protein, in addition to VEGF
165
and tissue inhibitor of
T. albolabris venom gland cDNA library. AL-B alpha was later derived metalloproteinase-3. KDR-bp binds to the extracellular domain of
using 3’-RACE based on the conserved sequence. In this study, purified KDR with a K
d
of 10
-8
M, resulting in specific blockade of endothelial
AL-B dimer agglutinated human platelets with the EC
50
of 180nM and cell growth induced by VEGF
165
. Inactive PLA
2
homologues are
was completely inhibited by anti GpIb antibody. MALDI ToF mass widely distributed in the venoms of Viperidae snakes and are known
spectroscopy found no glycosylation. The peptide mass fingerprints to act as myotoxins. To understand better the KDR and KDR-bp
were matched with deduced amino acid sequences of cloned genes. interaction, the authors resolved the binding region of KDR-bp using
AL-B alpha and beta contained 156 and 146 amino acids, respectively, eight synthetic peptides designed based on the structure of KDR-bp.
including 23-residue signal peptides. AL-B beta showed conserved A synthetic peptide based on the structure of the C-terminal loop
hydrophilic patches, which are putative sites for GpIb binding. The region of KDR-bp showed high affinity for KDR, but other peptides
authors propose that these three CLPs may function as bivalent did not, suggesting that the C-terminal loop region of KDR-bp is
adhesive proteins linking two GpIb molecules on adjacent platelets. ■ involved in the interaction with KDR. ■
EUROPEAN HAEMATOLOGY 11
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