4gln
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal Structure of Chemically Synthesized Heterochiral {D-Protein Antagonist plus VEGF-A} Protein Complex in space group P21/n== | |
| - | + | <StructureSection load='4gln' size='340' side='right' caption='[[4gln]], [[Resolution|resolution]] 1.60Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[4gln]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GLN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GLN FirstGlance]. <br> | |
| - | ==Disease== | + | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DAS:D-ASPARTIC+ACID'>DAS</scene>, <scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</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=DSG:D-ASPARAGINE'>DSG</scene>, <scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=DTH:D-THREONINE'>DTH</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qtk|3qtk]], [[4gls|4gls]], [[4glu|4glu]]</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=4gln FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gln OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gln RCSB], [http://www.ebi.ac.uk/pdbsum/4gln PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[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. | [[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. | ||
| - | + | == Function == | |
| - | ==Function== | + | |
[[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> | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically synthesized D- and L- forms of the protein ligand showed reciprocal chiral specificity in surface plasmon resonance binding experiments: The L-protein ligand bound only to D-VEGF-A, whereas the D-protein ligand bound only to L-VEGF-A. The D-protein ligand, but not the L-protein ligand, inhibited the binding of natural VEGF(165) to the VEGFR1 receptor. Racemic protein crystallography was used to determine the high resolution X-ray structure of the heterochiral complex consisting of {D-protein antagonist + L-protein form of VEGF-A}. Crystallization of a racemic mixture of these synthetic proteins in appropriate stoichiometry gave a racemic protein complex of more than 73 kDa containing six synthetic protein molecules. The structure of the complex was determined to a resolution of 1.6 A. Detailed analysis of the interaction between the D-protein antagonist and the VEGF-A protein molecule showed that the binding interface comprised a contact surface area of approximately 800 A(2) in accord with our design objectives, and that the D-protein antagonist binds to the same region of VEGF-A that interacts with VEGFR1-domain 2. | ||
| - | + | Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.,Mandal K, Uppalapati M, Ault-Riche D, Kenney J, Lowitz J, Sidhu SS, Kent SB Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):14779-84. doi:, 10.1073/pnas.1210483109. Epub 2012 Aug 27. PMID:22927390<ref>PMID:22927390</ref> | |
| - | + | ||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
==See Also== | ==See Also== | ||
*[[Vascular Endothelial Growth Factor|Vascular Endothelial Growth Factor]] | *[[Vascular Endothelial Growth Factor|Vascular Endothelial Growth Factor]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| - | [[Category: Ault-Riche, D | + | </StructureSection> |
| - | [[Category: Kenney, J | + | [[Category: Ault-Riche, D]] |
| - | [[Category: Kent, S B.H | + | [[Category: Kenney, J]] |
| - | [[Category: Lowitz, J | + | [[Category: Kent, S B.H]] |
| - | [[Category: Mandal, K | + | [[Category: Lowitz, J]] |
| - | [[Category: Sidhu, S | + | [[Category: Mandal, K]] |
| - | [[Category: Uppalapati, M | + | [[Category: Sidhu, S]] |
| + | [[Category: Uppalapati, M]] | ||
[[Category: D-protein antagonist]] | [[Category: D-protein antagonist]] | ||
[[Category: Growth factor-inhibitor complex]] | [[Category: Growth factor-inhibitor complex]] | ||
[[Category: Heterochiral protein-protein complex]] | [[Category: Heterochiral protein-protein complex]] | ||
Revision as of 18:32, 21 December 2014
Crystal Structure of Chemically Synthesized Heterochiral {D-Protein Antagonist plus VEGF-A} Protein Complex in space group P21/n
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