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PDBsum entry 1flt
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Complex (growth factor/transferase)
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PDB id
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1flt
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure at 1.7 a resolution of vegf in complex with domain 2 of the flt-1 receptor.
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Authors
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C.Wiesmann,
G.Fuh,
H.W.Christinger,
C.Eigenbrot,
J.A.Wells,
A.M.De vos.
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Ref.
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Cell, 1997,
91,
695-704.
[DOI no: ]
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PubMed id
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Abstract
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Vascular endothelial growth factor (VEGF) is a homodimeric hormone that induces
proliferation of endothelial cells through binding to the kinase domain receptor
and the Fms-like tyrosine kinase receptor (Flt-1), the extracellular portions of
which consist of seven immunoglobulin domains. We show that the second and third
domains of Flt-1 are necessary and sufficient for binding VEGF with near-native
affinity, and that domain 2 alone binds only 60-fold less tightly than
wild-type. The crystal structure of the complex between VEGF and the second
domain of Flt-1 shows domain 2 in a predominantly hydrophobic interaction with
the "poles" of the VEGF dimer. Based on this structure and on
mutational data, we present a model of VEGF bound to the first four domains of
Flt-1.
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Figure 2.
Figure 2. Ribbon Rendering of Flt-1[D2], in Two Views
Related by a Rotation of Approximately 90° about the
Vertical AxisThe termini and the secondary structure elements as
defined by the program Procheck ([26]) are labeled; β strands
are rendered as green arrows, the helical turn as a green
ribbon, and the loop regions as gray tubes. The disulfide bond
is shown in ball-and-stick rendering, with sulfur atoms colored
yellow. The two potential N-linked glycosylation sites at
Asn-164 and Asn-196 are colored blue. The VEGF binding site is
located on the “bottom” end of the five-stranded sheet;
residues in contact with VEGF in the complex are colored red. A
segment near the N terminus, which forms strand βa in members
of the I set of the immunoglobulin superfamily, bulges away from
the core of the domain. This figure was created using the
program MOLMOL ( [24]).
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Figure 3.
Figure 3. Stereo Views in Ball-and-Stick Rendering of
Structural DetailsHydrogen bonds are shown as dotted lines;
oxygen atoms are colored red, nitrogens dark blue, and carbons
gray. This figure was generated using the programs MOLSCRIPT
([25]) and RASTER3D ( [29]).(A) The environment of Phe-135 of
Flt-1.(B) The region in Flt-1 corresponding to the “Y
corner” found in most Greek key barrel proteins.(C) A region
of the interface between VEGF (in dark gray) and Flt-1 (in light
gray) around the interaction between Asp-63 and Arg-224, showing
a chain of water molecules in the interface.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(1997,
91,
695-704)
copyright 1997.
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