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| - | {{STRUCTURE_3qtk| PDB=3qtk | SCENE= }} | |
| - | ===The crystal structure of chemically synthesized VEGF-A=== | |
| - | {{ABSTRACT_PUBMED_21744452}} | |
| | | | |
| - | ==Disease== | + | ==The crystal structure of chemically synthesized VEGF-A== |
| - | [[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[http://omim.org/entry/603933 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. | + | <StructureSection load='3qtk' size='340' side='right'caption='[[3qtk]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[3qtk]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QTK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QTK FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.849Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TFA:TRIFLUOROACETIC+ACID'>TFA</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qtk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qtk OCA], [https://pdbe.org/3qtk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qtk RCSB], [https://www.ebi.ac.uk/pdbsum/3qtk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qtk ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[https://omim.org/entry/603933 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 == |
| | + | [https://www.uniprot.org/uniprot/VEGFA_HUMAN 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.<ref>PMID:11427521</ref> <ref>PMID:15520188</ref> <ref>PMID:16489009</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Efficient access: The 204-residue covalent-dimer vascular endothelial growth factor (VEGF, see picture) with full mitogenic activity was prepared from three unprotected peptide segments by one-pot native chemical ligations. The covalent structure of the synthetic VEGF was confirmed by precise mass measurement, and the three-dimensional structure of the synthetic protein was determined by high-resolution X-ray crystallography. |
| | | | |
| - | ==Function==
| + | Total chemical synthesis of biologically active vascular endothelial growth factor.,Mandal K, Kent SB Angew Chem Int Ed Engl. 2011 Aug 22;50(35):8029-33. doi: 10.1002/anie.201103237. , Epub 2011 Jul 8. PMID:21744452<ref>PMID:21744452</ref> |
| - | [[http://www.uniprot.org/uniprot/VEGFA_HUMAN 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.<ref>PMID:11427521</ref><ref>PMID:15520188</ref><ref>PMID:16489009</ref>
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[3qtk]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QTK OCA].
| + | </div> |
| | + | <div class="pdbe-citations 3qtk" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Vascular Endothelial Growth Factor|Vascular Endothelial Growth Factor]] | + | *[[VEGF 3D Structures|VEGF 3D Structures]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:021744452</ref><references group="xtra"/><references/>
| + | __TOC__ |
| - | [[Category: Kent, S B.H.]] | + | </StructureSection> |
| - | [[Category: Mandal, K.]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Covalent dimer]] | + | [[Category: Large Structures]] |
| - | [[Category: Cysteine knot protein]] | + | [[Category: Kent SBH]] |
| - | [[Category: Growth factor]]
| + | [[Category: Mandal K]] |
| - | [[Category: Hormone]]
| + | |
| - | [[Category: Human vegf-a]]
| + | |
| - | [[Category: X-ray crystal structure]]
| + | |
| 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 PubMed
Efficient access: The 204-residue covalent-dimer vascular endothelial growth factor (VEGF, see picture) with full mitogenic activity was prepared from three unprotected peptide segments by one-pot native chemical ligations. The covalent structure of the synthetic VEGF was confirmed by precise mass measurement, and the three-dimensional structure of the synthetic protein was determined by high-resolution X-ray crystallography.
Total chemical synthesis of biologically active vascular endothelial growth factor.,Mandal K, Kent SB Angew Chem Int Ed Engl. 2011 Aug 22;50(35):8029-33. doi: 10.1002/anie.201103237. , Epub 2011 Jul 8. PMID:21744452[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Murphy JF, Fitzgerald DJ. Vascular endothelial growth factor induces cyclooxygenase-dependent proliferation of endothelial cells via the VEGF-2 receptor. FASEB J. 2001 Jul;15(9):1667-9. PMID:11427521
- ↑ Woolard J, Wang WY, Bevan HS, Qiu Y, Morbidelli L, Pritchard-Jones RO, Cui TG, Sugiono M, Waine E, Perrin R, Foster R, Digby-Bell J, Shields JD, Whittles CE, Mushens RE, Gillatt DA, Ziche M, Harper SJ, Bates DO. VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression. Cancer Res. 2004 Nov 1;64(21):7822-35. PMID:15520188 doi:10.1158/0008-5472.CAN-04-0934
- ↑ Dixelius J, Olsson AK, Thulin A, Lee C, Johansson I, Claesson-Welsh L. Minimal active domain and mechanism of action of the angiogenesis inhibitor histidine-rich glycoprotein. Cancer Res. 2006 Feb 15;66(4):2089-97. PMID:16489009 doi:10.1158/0008-5472.CAN-05-2217
- ↑ Mandal K, Kent SB. Total Chemical Synthesis of Biologically Active Vascular Endothelial Growth Factor. Angew Chem Int Ed Engl. 2011 Jul 8. doi: 10.1002/anie.201103237. PMID:21744452 doi:10.1002/anie.201103237
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