Source:http://linkedlifedata.com/resource/pubmed/id/18251716
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2008-4-9
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| pubmed:abstractText |
VEGF (vascular endothelial growth factor) regulates neovascularization through binding to its receptor KDR (kinase insert domain-containing receptor; VEGF receptor-2). We recently identified a catalytically inactive PLA(2) (phospholipase A(2)) homologue (KDR-bp) in the venom of eastern cottonmouth (Agkistrodon piscivorus piscivorus) as a third KDR-binding protein, in addition to VEGF(165) and tissue inhibitor of metalloproteinase-3. KDR-bp binds to the extracellular domain of KDR with a K(d) of 10(-8) M, resulting in specific blockade of endothelial cell growth induced by VEGF(165). Inactive PLA(2) homologues are widely distributed in the venoms of Viperidae snakes and are known to act as myotoxins. In the present study, we demonstrated that KDR-binding ability is a common characteristic for inactive PLA(2) homologues in snake venom, but not for active PLA(2)s such as neurotoxic and platelet aggregation-modulating PLA(2)s. To understand better the KDR and KDR-bp interaction, we resolved the binding region of KDR-bp using eight synthetic peptides designed based on the structure of KDR-bp. A synthetic peptide based on the structure of the C-terminal loop region of KDR-bp showed high affinity for KDR, but other peptides did not, suggesting that the C-terminal loop region of KDR-bp is involved in the interaction with KDR. The results of the present study provide insight into the binding of inactive PLA(2) homologues to KDR, and may also assist in the design of novel anti-KDR molecules for anti-angiogenic therapy.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1470-8728
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
411
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
515-22
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:18251716-Amino Acid Sequence,
pubmed-meshheading:18251716-Animals,
pubmed-meshheading:18251716-Binding Sites,
pubmed-meshheading:18251716-Catalysis,
pubmed-meshheading:18251716-Conserved Sequence,
pubmed-meshheading:18251716-Enzyme Activation,
pubmed-meshheading:18251716-Models, Molecular,
pubmed-meshheading:18251716-Molecular Sequence Data,
pubmed-meshheading:18251716-Peptides,
pubmed-meshheading:18251716-Phospholipases A2,
pubmed-meshheading:18251716-Protein Binding,
pubmed-meshheading:18251716-Protein Structure, Tertiary,
pubmed-meshheading:18251716-Sequence Alignment,
pubmed-meshheading:18251716-Snake Venoms,
pubmed-meshheading:18251716-Static Electricity,
pubmed-meshheading:18251716-Surface Plasmon Resonance,
pubmed-meshheading:18251716-Vascular Endothelial Growth Factor Receptor-2
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
Catalytically inactive phospholipase A2 homologue binds to vascular endothelial growth factor receptor-2 via a C-terminal loop region.
|
| pubmed:affiliation |
Department of Biochemistry, Meiji Pharmaceutical University, 2-522-1 Kiyose, Tokyo 204-8588, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|