6zfl
From Proteopedia
(Difference between revisions)
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==High resolution structure of VEGF-A 12:107 crystallized in tetragonal form== | ==High resolution structure of VEGF-A 12:107 crystallized in tetragonal form== | ||
| - | <StructureSection load='6zfl' size='340' side='right'caption='[[6zfl]]' scene=''> | + | <StructureSection load='6zfl' size='340' side='right'caption='[[6zfl]], [[Resolution|resolution]] 1.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZFL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6zfl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZFL FirstGlance]. <br> |
| - | </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=6zfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zfl OCA], [https://pdbe.org/6zfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zfl RCSB], [https://www.ebi.ac.uk/pdbsum/6zfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zfl ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6zcd|6zcd]], [[6z3f|6z3f]], [[6z13|6z13]], [[6zbr|6zbr]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VEGFA, VEGF ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6zfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zfl OCA], [https://pdbe.org/6zfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zfl RCSB], [https://www.ebi.ac.uk/pdbsum/6zfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zfl ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | Macrocyclization constraints are widely used in the design of protein ligands to stabilize their bioactive conformation and increase their affinities. However, the resulting changes in binding entropy can be puzzling and uncorrelated to affinity gains. Here we report the thermodynamic (Isothermal Titration Calorimetry) and structural (X-ray, NMR and CD) analysis of a complete series of lactam-bridged peptide ligands of the vascular endothelial growth factor, and their unconstrained analogs. We show that differences in thermodynamics arise mainly from the folding energy of the peptide upon binding. The systematic reduction in conformational entropy penalty due to helix pre-organization can be counterbalanced by an unfavorable vibrational entropy change if the constraints are too rigid. The gain in configurational entropy partially escapes the enthalpy/entropy compensation and leads to an improvement in affinity. The precision of the analytical ITC method makes this study a possible benchmark for constrained peptides optimization. | ||
| + | |||
| + | Structural and ITC Characterization of Peptide-Protein Binding: Thermodynamic Consequences of Cyclization Constraints, a Case Study on Vascular Endothelial Growth Factor Ligands.,Gaucher JF, Reille-Seroussi M, Broussy S Chemistry. 2022 Jun 5. doi: 10.1002/chem.202200465. PMID:35665969<ref>PMID:35665969</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6zfl" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Mannosidase 3D structures|Mannosidase 3D structures]] | ||
| + | *[[VEGF 3D Structures|VEGF 3D Structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Broussy S]] | + | [[Category: Broussy, S]] |
| - | [[Category: Gaucher J | + | [[Category: Gaucher, J F]] |
| - | [[Category: Reille-Seroussi M]] | + | [[Category: Reille-Seroussi, M]] |
| + | [[Category: Growth factor]] | ||
| + | [[Category: Signaling protein]] | ||
Revision as of 16:19, 6 July 2022
High resolution structure of VEGF-A 12:107 crystallized in tetragonal form
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