7ll9: Difference between revisions

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-'''Unreleased structure'''
-The entry 7ll9 is ON HOLD
+==D-Protein RFX-V2 Bound to the VEGFR1 Domain 3 Site on VEGF-A==
+<StructureSection load='7ll9' size='340' side='right'caption='[[7ll9]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7ll9]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LL9 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]] 2.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=DAS:D-ASPARTIC+ACID'>DAS</scene>, <scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=DGN:D-GLUTAMINE'>DGN</scene>, <scene name='pdbligand=DHI:D-HISTIDINE'>DHI</scene>, <scene name='pdbligand=DIL:D-ISOLEUCINE'>DIL</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=DLY:D-LYSINE'>DLY</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=DSG:D-ASPARAGINE'>DSG</scene>, <scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=DVA:D-VALINE'>DVA</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=7ll9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ll9 OCA], [https://pdbe.org/7ll9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ll9 RCSB], [https://www.ebi.ac.uk/pdbsum/7ll9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ll9 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 ==
+We report a general approach to engineering multivalent d-proteins with antibody-like activities in vivo. Mirror-image phage display and structure-guided design were utilized to create a d-protein that uses receptor mimicry to antagonize vascular endothelial growth factor A (VEGF-A). Selections against the d-protein form of VEGF-A using phage-displayed libraries of two different domain scaffolds yielded two proteins that bound distinct receptor interaction sites on VEGF-A. X-ray crystal structures of the d-protein/VEGF-A complexes were used to guide affinity maturation and to construct a heterodimeric d-protein VEGF-A antagonist with picomolar activity. The d-protein VEGF-A antagonist prevented vascular leakage in a rabbit eye model of wet age-related macular degeneration and slowed tumor growth in the MC38 syngeneic mouse tumor model with efficacies comparable to those of approved antibody drugs, and in contrast with antibodies, the d-protein was non-immunogenic during treatment and following subcutaneous immunizations.
-Authors: Marinec, P.S., Landgraf, K.E., Uppalapati, M., Chen, G., Xie, D., Jiang, Q., Zhao, Y., Petriello, A., Deshayes, K., Kent, S.B.H., Ault-Riche, D., Sidhu, S.S.
+A Non-immunogenic Bivalent d-Protein Potently Inhibits Retinal Vascularization and Tumor Growth.,Marinec PS, Landgraf KE, Uppalapati M, Chen G, Xie D, Jiang Q, Zhao Y, Petriello A, Deshayes K, Kent SBH, Ault-Riche D, Sidhu SS ACS Chem Biol. 2021 Mar 19;16(3):548-556. doi: 10.1021/acschembio.1c00017. Epub , 2021 Feb 23. PMID:33621466<ref>PMID:33621466</ref>
-Description: D-Protein RFX-V2 Bound to the VEGFR1 Domain 3 Site on VEGF-A
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Uppalapati, M]]
+<div class="pdbe-citations 7ll9" style="background-color:#fffaf0;"></div>
-[[Category: Deshayes, K]]
-[[Category: Ault-Riche, D]]
+==See Also==
-[[Category: Zhao, Y]]
+*[[VEGF 3D Structures|VEGF 3D Structures]]
-[[Category: Xie, D]]
+== References ==
-[[Category: Sidhu, S.S]]
+<references/>
-[[Category: Landgraf, K.E]]
+__TOC__
-[[Category: Jiang, Q]]
+</StructureSection>
-[[Category: Chen, G]]
+[[Category: Homo sapiens]]
-[[Category: Marinec, P.S]]
+[[Category: Large Structures]]
-[[Category: Petriello, A]]
+[[Category: Synthetic construct]]
-[[Category: Kent, S.B.H]]
+[[Category: Ault-Riche D]]
+[[Category: Chen G]]
+[[Category: Deshayes K]]
+[[Category: Jiang Q]]
+[[Category: Kent SBH]]
+[[Category: Landgraf KE]]
+[[Category: Marinec PS]]
+[[Category: Petriello A]]
+[[Category: Sidhu SS]]
+[[Category: Uppalapati M]]
+[[Category: Xie D]]
+[[Category: Zhao Y]]