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- PDB-2vpf: VASCULAR ENDOTHELIAL GROWTH FACTOR REFINED TO 1.93 ANGSTROMS RESO... -

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Basic information

Entry
Database: PDB / ID: 2vpf
TitleVASCULAR ENDOTHELIAL GROWTH FACTOR REFINED TO 1.93 ANGSTROMS RESOLUTION
ComponentsVASCULAR ENDOTHELIAL GROWTH FACTOR
KeywordsGROWTH FACTOR / CYSTINE KNOT / ANGIOGENESIS / VASCULOGENESIS
Function / homology
Function and homology information


basophil chemotaxis / positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway / cellular stress response to acid chemical / VEGF-A complex / Signaling by VEGF / lymph vessel morphogenesis / positive regulation of lymphangiogenesis / negative regulation of adherens junction organization / vascular endothelial growth factor receptor 1 binding / negative regulation of establishment of endothelial barrier ...basophil chemotaxis / positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway / cellular stress response to acid chemical / VEGF-A complex / Signaling by VEGF / lymph vessel morphogenesis / positive regulation of lymphangiogenesis / negative regulation of adherens junction organization / vascular endothelial growth factor receptor 1 binding / negative regulation of establishment of endothelial barrier / vascular endothelial growth factor receptor binding / VEGF ligand-receptor interactions / positive regulation of mast cell chemotaxis / post-embryonic camera-type eye development / primitive erythrocyte differentiation / positive regulation of protein kinase C signaling / positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway / negative regulation of blood-brain barrier permeability / VEGF-activated neuropilin signaling pathway / bone trabecula formation / positive regulation of vascular endothelial growth factor signaling pathway / coronary vein morphogenesis / cardiac vascular smooth muscle cell development / lung vasculature development / lymphangiogenesis / eye photoreceptor cell development / positive regulation of trophoblast cell migration / endothelial cell chemotaxis / motor neuron migration / positive regulation of epithelial tube formation / vascular endothelial growth factor receptor-2 signaling pathway / VEGF binds to VEGFR leading to receptor dimerization / regulation of nitric oxide mediated signal transduction / positive regulation of axon extension involved in axon guidance / vascular wound healing / positive regulation of protein localization to early endosome / regulation of hematopoietic progenitor cell differentiation / positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis / positive regulation of branching involved in ureteric bud morphogenesis / camera-type eye morphogenesis / neuropilin binding / induction of positive chemotaxis / coronary artery morphogenesis / negative regulation of cell-cell adhesion mediated by cadherin / vascular endothelial growth factor receptor 2 binding / positive regulation of vascular permeability / tube formation / dopaminergic neuron differentiation / commissural neuron axon guidance / negative regulation of epithelial to mesenchymal transition / platelet-derived growth factor receptor binding / surfactant homeostasis / extracellular matrix binding / cell migration involved in sprouting angiogenesis / cardiac muscle cell development / epithelial cell maturation / sprouting angiogenesis / positive regulation of positive chemotaxis / endothelial cell proliferation / Regulation of gene expression by Hypoxia-inducible Factor / positive regulation of leukocyte migration / vascular endothelial growth factor signaling pathway / positive regulation of p38MAPK cascade / positive regulation of endothelial cell chemotaxis / artery morphogenesis / retinal ganglion cell axon guidance / branching involved in blood vessel morphogenesis / positive regulation of cell migration involved in sprouting angiogenesis / positive regulation of DNA biosynthetic process / positive regulation of neuroblast proliferation / positive chemotaxis / negative regulation of fat cell differentiation / transmembrane receptor protein tyrosine kinase activator activity / positive regulation of sprouting angiogenesis / chemoattractant activity / outflow tract morphogenesis / positive regulation of focal adhesion assembly / mesoderm development / monocyte differentiation / positive regulation of receptor internalization / macrophage differentiation / positive regulation of cell division / fibronectin binding / positive regulation of cell adhesion / neuroblast proliferation / positive regulation of blood vessel endothelial cell migration / cellular response to vascular endothelial growth factor stimulus / mammary gland alveolus development / vasculogenesis / positive regulation of osteoblast differentiation / vascular endothelial growth factor receptor signaling pathway / heart morphogenesis / ovarian follicle development / cell maturation / homeostasis of number of cells within a tissue / positive regulation of protein autophosphorylation / positive regulation of endothelial cell proliferation / epithelial cell differentiation / lactation / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
Similarity search - Function
Vascular endothelial growth factor, heparin-binding domain / Vascular endothelial growth factor, heparin-binding domain superfamily / VEGF heparin-binding domain / PDGF/VEGF domain / Platelet-derived growth factor, conserved site / PDGF/VEGF domain / Platelet-derived growth factor (PDGF) family signature. / Platelet-derived growth factor (PDGF) family profile. / Platelet-derived and vascular endothelial growth factors (PDGF, VEGF) family / Cystine Knot Cytokines, subunit B ...Vascular endothelial growth factor, heparin-binding domain / Vascular endothelial growth factor, heparin-binding domain superfamily / VEGF heparin-binding domain / PDGF/VEGF domain / Platelet-derived growth factor, conserved site / PDGF/VEGF domain / Platelet-derived growth factor (PDGF) family signature. / Platelet-derived growth factor (PDGF) family profile. / Platelet-derived and vascular endothelial growth factors (PDGF, VEGF) family / Cystine Knot Cytokines, subunit B / Cystine-knot cytokines / Cystine-knot cytokine / Ribbon / Mainly Beta
Similarity search - Domain/homology
Vascular endothelial growth factor A, long form
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.93 Å
AuthorsMuller, Y.A. / De Vos, A.M.
Citation
Journal: Structure / Year: 1997
Title: The crystal structure of vascular endothelial growth factor (VEGF) refined to 1.93 A resolution: multiple copy flexibility and receptor binding.
Authors: Muller, Y.A. / Christinger, H.W. / Keyt, B.A. / de Vos, A.M.
#1: Journal: Proc.Natl.Acad.Sci.USA / Year: 1997
Title: Vascular Endothelial Growth Factor: Crystal Structure and Functional Mapping of the Kinase Domain Receptor Binding Site
Authors: Muller, Y.A. / Li, B. / Christinger, H.W. / Wells, J.A. / Cunningham, B.C. / De Vos, A.M.
#2: Journal: Proteins / Year: 1996
Title: Crystallization of the Receptor Binding Domain of Vascular Endothelial Growth Factor
Authors: Christinger, H.W. / Muller, Y.A. / Berleau, L.T. / Keyt, B.A. / Cunningham, B.C. / Ferrara, N. / De Vos, A.M.
History
DepositionJul 29, 1997Processing site: BNL
Revision 1.0Jul 29, 1998Provider: repository / Type: Initial release
Revision 1.1Mar 25, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Aug 9, 2023Group: Database references / Refinement description / Category: database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: VASCULAR ENDOTHELIAL GROWTH FACTOR
B: VASCULAR ENDOTHELIAL GROWTH FACTOR
C: VASCULAR ENDOTHELIAL GROWTH FACTOR
D: VASCULAR ENDOTHELIAL GROWTH FACTOR
E: VASCULAR ENDOTHELIAL GROWTH FACTOR
F: VASCULAR ENDOTHELIAL GROWTH FACTOR
G: VASCULAR ENDOTHELIAL GROWTH FACTOR
H: VASCULAR ENDOTHELIAL GROWTH FACTOR


Theoretical massNumber of molelcules
Total (without water)95,5898
Polymers95,5898
Non-polymers00
Water11,530640
1
C: VASCULAR ENDOTHELIAL GROWTH FACTOR
D: VASCULAR ENDOTHELIAL GROWTH FACTOR


Theoretical massNumber of molelcules
Total (without water)23,8972
Polymers23,8972
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2610 Å2
ΔGint-24 kcal/mol
Surface area11200 Å2
MethodPISA
2
A: VASCULAR ENDOTHELIAL GROWTH FACTOR
B: VASCULAR ENDOTHELIAL GROWTH FACTOR


Theoretical massNumber of molelcules
Total (without water)23,8972
Polymers23,8972
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2680 Å2
ΔGint-25 kcal/mol
Surface area11570 Å2
MethodPISA
3
E: VASCULAR ENDOTHELIAL GROWTH FACTOR
F: VASCULAR ENDOTHELIAL GROWTH FACTOR


Theoretical massNumber of molelcules
Total (without water)23,8972
Polymers23,8972
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2660 Å2
ΔGint-26 kcal/mol
Surface area11670 Å2
MethodPISA
4
G: VASCULAR ENDOTHELIAL GROWTH FACTOR
H: VASCULAR ENDOTHELIAL GROWTH FACTOR


Theoretical massNumber of molelcules
Total (without water)23,8972
Polymers23,8972
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2730 Å2
ΔGint-26 kcal/mol
Surface area11140 Å2
MethodPISA
Unit cell
Length a, b, c (Å)45.470, 68.470, 85.820
Angle α, β, γ (deg.)105.44, 93.71, 101.49
Int Tables number1
Space group name H-MP1
Noncrystallographic symmetry (NCS)NCS oper:
IDCodeMatrixVector
1given(-0.34321, -0.52364, -0.77974), (-0.53222, -0.57561, 0.62082), (-0.77391, 0.62807, -0.08114)-1.08611, 0.54147, -1.1872
2given(0.00287, -0.22, -0.9755), (0.4764, 0.85798, -0.1921), (0.87922, -0.46418, 0.10727)62.53261, -0.08027, 5.22423
3given(-0.91736, 0.01658, 0.3977), (0.27428, -0.69774, 0.66176), (0.28847, 0.71615, 0.63554)-29.25429, -26.73726, -49.50043
4given(0.36141, 0.27047, 0.89232), (0.2573, -0.94878, 0.18337), (0.8962, 0.16332, -0.41248)-41.65716, -19.30638, 5.22588
5given(-0.95462, 0.29008, -0.0675), (0.21043, 0.49658, -0.8421), (-0.21075, -0.81809, -0.53508)18.67854, 37.36586, 18.51475
6given(0.86923, -0.4668, -0.16292), (-0.46869, -0.88288, 0.02903), (-0.15739, 0.05112, -0.98621)-3.92029, 36.54798, 22.71535
7given(0.09535, 0.60375, 0.79145), (-0.32205, 0.77103, -0.54936), (-0.94191, -0.20251, 0.26795)-37.17354, -2.72744, 21.8472

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Components

#1: Protein
VASCULAR ENDOTHELIAL GROWTH FACTOR / VEGF / VASCULAR PERMEABILITY FACTOR / VPF


Mass: 11948.680 Da / Num. of mol.: 8 / Fragment: RECEPTOR BINDING DOMAIN, RESIDUES 8 - 109
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cellular location (production host): CYTOPLASM / Production host: Escherichia coli (E. coli) / References: UniProt: P15692
#2: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 640 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.7 Å3/Da / Density % sol: 54 %
Crystal growMethod: vapor diffusion, hanging drop / pH: 5.6
Details: HANGING DROP, CRYSTALLIZED FROM 14 % PEG3350, 10% ISOPROPANOL, 0.2 M AMMONIUM ACETATE PH 5.6, vapor diffusion - hanging drop
Crystal
*PLUS
Crystal grow
*PLUS
pH: 7.5 / Method: vapor diffusion, sitting drop
Components of the solutions
*PLUS
IDConc.Common nameCrystal-IDSol-IDChemical formula
115 mg/mlprotein1drop
220 mMTris-HCl1drop
30.4 M1dropNaCl
414 %PEG33501reservoir
510 %isopropanol1reservoir
60.2 Mammonium sulfate1reservoir

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: CHESS / Beamline: F1 / Wavelength: 0.918
DetectorType: PRINCETON 2K / Detector: CCD / Date: Mar 1, 1996
RadiationMonochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.918 Å / Relative weight: 1
ReflectionResolution: 1.9→20 Å / Num. obs: 72050 / % possible obs: 94 % / Redundancy: 2.5 % / Rmerge(I) obs: 0.044 / Net I/σ(I): 9.4
Reflection shellResolution: 1.9→2 Å / Redundancy: 1.5 % / Rsym value: 0.127 / % possible all: 80.8
Reflection
*PLUS
Num. measured all: 180803
Reflection shell
*PLUS
% possible obs: 81 % / Rmerge(I) obs: 0.127

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Processing

Software
NameClassification
DENZOdata reduction
SCALEPACKdata scaling
X-PLORmodel building
REFMACrefinement
X-PLORrefinement
X-PLORphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1VPF
Resolution: 1.93→16 Å / Cross valid method: THROUGHOUT
Details: AN EXPLICIT BULK SOLVENT MASK WAS CALCULATED WITH PROGRAM X-PLOR AND INTRODUCED INTO REFMAC USING PARTIAL STRUCTURE FACTORS (F-PART)
RfactorNum. reflection% reflectionSelection details
Rfree0.272 7074 10 %RESOLUTION SHELLS
Rwork0.209 ---
obs-68901 94 %-
Displacement parametersBiso mean: 47.1 Å2
Baniso -1Baniso -2Baniso -3
1--8.56 Å20.76 Å21.22 Å2
2--3.09 Å21.64 Å2
3---5.47 Å2
Refine analyzeLuzzati sigma a obs: 0.19 Å
Refinement stepCycle: LAST / Resolution: 1.93→16 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6142 0 0 640 6782
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONp_bond_d0.0110.02
X-RAY DIFFRACTIONp_angle_d0.030.04
X-RAY DIFFRACTIONp_angle_deg
X-RAY DIFFRACTIONp_planar_d0.0320.05
X-RAY DIFFRACTIONp_hb_or_metal_coord
X-RAY DIFFRACTIONp_mcbond_it2.012.5
X-RAY DIFFRACTIONp_mcangle_it2.7784
X-RAY DIFFRACTIONp_scbond_it2.4682.5
X-RAY DIFFRACTIONp_scangle_it3.8924
X-RAY DIFFRACTIONp_plane_restr
X-RAY DIFFRACTIONp_chiral_restr0.1130.15
X-RAY DIFFRACTIONp_singtor_nbd0.1790.3
X-RAY DIFFRACTIONp_multtor_nbd0.2430.3
X-RAY DIFFRACTIONp_xhyhbond_nbd
X-RAY DIFFRACTIONp_xyhbond_nbd0.1890.3
X-RAY DIFFRACTIONp_planar_tor4.17
X-RAY DIFFRACTIONp_staggered_tor18.215
X-RAY DIFFRACTIONp_orthonormal_tor
X-RAY DIFFRACTIONp_transverse_tor29.920
X-RAY DIFFRACTIONp_special_tor
Software
*PLUS
Name: REFMAC / Classification: refinement
Refinement
*PLUS
Num. reflection all: 68901 / Rfactor obs: 0.209
Solvent computation
*PLUS
Displacement parameters
*PLUS

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