5fv2: Difference between revisions
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==Crystal structure of hVEGF in complex with VH domain antibody== | ==Crystal structure of hVEGF in complex with VH domain antibody== | ||
<StructureSection load='5fv2' size='340' side='right' caption='[[5fv2]], [[Resolution|resolution]] 3.45Å' scene=''> | <StructureSection load='5fv2' size='340' side='right'caption='[[5fv2]], [[Resolution|resolution]] 3.45Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5fv2]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FV2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5fv2]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FV2 FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fv1|5fv1]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fv1|5fv1]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fv2 OCA], [http://pdbe.org/5fv2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fv2 RCSB], [http://www.ebi.ac.uk/pdbsum/5fv2 PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fv2 OCA], [http://pdbe.org/5fv2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fv2 RCSB], [http://www.ebi.ac.uk/pdbsum/5fv2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fv2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5fv2" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5fv2" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Vascular Endothelial Growth Factor|Vascular Endothelial Growth Factor]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Batuwangala, T]] | [[Category: Batuwangala, T]] | ||
[[Category: Chung, C]] | [[Category: Chung, C]] | ||
Revision as of 11:03, 21 May 2019
Crystal structure of hVEGF in complex with VH domain antibodyCrystal structure of hVEGF in complex with VH domain antibody
Structural highlights
Disease[VEGFA_HUMAN] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:603933]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Function[VEGFA_HUMAN] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.[1] [2] [3] Publication Abstract from PubMedA potent VEGF inhibitor with novel antibody architecture and antigen binding mode has been developed. The molecule, hereafter referred to as VEGF dual dAba (domain antibody), was evaluated in vitro for binding to VEGF and for potency in VEGF driven models and compared with other anti-VEGF biologics that have been used in ocular anti-angiogenic therapeutic regimes. VEGF dual dAb is more potent than bevacizumab and ranibizumab for VEGF binding and inhibition of VEGF RBAb (receptor binding assay) formats and when compared using in vitro models of angiogenesis; and displays comparable inhibition to aflibercept, (Eylea). VEGF dual dAb is dimeric and each monomer contains two distinct anti-VEGF domain antibodies attached via linkers to a human IgG1 Fc domain. Mechanistically, the enhanced in vitro potency of VEGF dual dAb in comparison to other anti-VEGF biologics can be explained by increased binding stoichiometry. A consistent model of the target engagement has been built based on the X-ray complexes of each of the two isolated domain antibodies with the VEGF antigen. Novel interaction mechanism of a domain antibody based inhibitor of human vascular endothelial growth factor with greater potency than ranibizumab and bevacizumab and improved capacity over aflibercept.,Walker A, Chung CW, Neu M, Burman M, Batuwangala T, Jones G, Tang CM, Steward M, Mullin M, Tournier N, Lewis A, Korczynska J, Chung V, Catchpole I J Biol Chem. 2016 Jan 4. pii: jbc.M115.691162. PMID:26728464[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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