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PDBsum entry 4gls
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Growth factor/inhibitor
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PDB id
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4gls
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Contents |
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95 a.a.
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56 a.a.
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56 a.a.
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95 a.a.
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PDB id:
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| Name: |
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Growth factor/inhibitor
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Title:
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Crystal structure of chemically synthesized heterochiral {d-protein antagonist plus vegf-a} protein complex in space group p21
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Structure:
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D- vascular endothelial growth factor-a. Chain: a, b. Engineered: yes. L- rfx001. Chain: c, g. Engineered: yes. D- rfx001. Chain: d, h. Engineered: yes.
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Source:
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Synthetic: yes. Other_details: chemical synthesis. Homo sapiens. Human. Organism_taxid: 9606. Other_details: chemical synthesis
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Resolution:
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1.60Å
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R-factor:
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0.192
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R-free:
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0.231
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Authors:
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K.Mandal,M.Uppalapati,D.Ault-Riche,J.Kenney,J.Lowitz,S.Sidhu, S.B.H.Kent
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Key ref:
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K.Mandal
et al.
(2012).
Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.
Proc Natl Acad Sci U S A,
109,
14779-14784.
PubMed id:
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Date:
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14-Aug-12
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Release date:
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05-Sep-12
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PROCHECK
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Headers
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References
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No UniProt id for this chain
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No UniProt id for this chain
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Proc Natl Acad Sci U S A
109:14779-14784
(2012)
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PubMed id:
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Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.
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K.Mandal,
M.Uppalapati,
D.Ault-Riché,
J.Kenney,
J.Lowitz,
S.S.Sidhu,
S.B.Kent.
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ABSTRACT
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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 Å. 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 Å(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.
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