4ag8

CRYSTAL STRUCTURE OF THE VEGFR2 KINASE DOMAIN IN COMPLEX WITH AXITINIB (AG-013736) (N-Methyl-2-(3-((E)-2-pyridin-2-yl-vinyl)-1H- indazol-6-ylsulfanyl)-benzamide)

Method: X-RAY DIFFRACTION Dmax: 72.0 Å Quality: GOOD

1. Protein Identity and Related Structures Protein Identity & Related Structures

VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2

HOMO SAPIENS

UniProt P35968

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Protein monomer Monomer Protein × 1 PDB declaration: monomeric(1) Consistent with protein copy count Chain A; UniProt 806–939 Chain A; UniProt 990–1171 Fragment:KINASE DOMAIN, RESIDUES 806-940,990-1171 Mutation:YES AXI AXITINIB × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION, HANGING DROP;pH 7.5;CRYSTALS WERE GROWN AT 4 OR 13 C BY THE HANGING DROP VAPOR DIFFUSION BY MIXING 2 MICORLITERS OF PROTEIN-INHIBITOR COMPLEX SOLUTION WITH 2 MICROLITERS OF MOTHER LIQUOR (100 MM HEPES (PH 7.5), 200 MM AMMONIUM SULFATE, 5% (V/V) MPD, AND 15-20% (W/V) POLYETHYLENE GLYCOL (MW = 6000)). BEFORE SEALING THE COVERSLIPS ABOVE THE RESERVOIRS, BETA-MERCAPTOETHANOL WAS ADDED TO THE RESERVOIRS TO A FINAL CONCENTRATION OF 60 MM. THIS PROCEDURE PRODUCED MICROCRYSTALS THAT WERE SUBSEQUENTLY USED TO SEED MORE CRYSTALLIZATION DROPS AFTER 12-18 HOURS OF EQUILIBRATION. Resolution 1.95 Å R-free 0.241

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

53 other PDB entries and 64 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name VGFR2_HUMAN
Isoform
PDB entities 1
Chains and sequence ranges Author chain A; PDBConstruct 1–134; UniProt 806–939 Author chain A; PDBConstruct 135–316; UniProt 990–1171

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

SAXS scattering curve SAXS Profile

SAXS profile for 4ag8

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 4ag8
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2. Structure Basics 2. Structure Basics

Entry ID entry_id4ag8
Deposition date deposition_date2012-01-24
Structure title titleCRYSTAL STRUCTURE OF THE VEGFR2 KINASE DOMAIN IN COMPLEX WITH AXITINIB (AG-013736) (N-Methyl-2-(3-((E)-2-pyridin-2-yl-vinyl)-1H- indazol-6-ylsulfanyl)-benzamide)
Keywords keywordsTRANSFERASE, ANGIOGENESIS, NUCLEOTIDE-BINDING, INHIBITOR, PHOSPHORYLATION, TRANSMEMBRANE; TRANSFERASE
Experimental Method methodX-RAY DIFFRACTION

3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier20.62
Radius of gyration Rg (electron density) rg_electron19.53
Forward intensity I(0) i019596000.00
Molecular weight molecular_weight34238.0 kDa
Excluded volume excluded_volume43145 ų
Envelope volume envelope_volume50397 ų
Hydration-shell volume shell_volume21300 ų
Envelope diameter envelope_diameter65.7
Shell Rg shell_rg26.13
Envelope Rg envelope_rg19.81
Shape Rg shape_rg19.53
Total Rg total_rg20.44
Total atoms total_atoms2409
Residues n_residues296
Spherical-harmonic order n_harmonics20
q range q_range— – 0.5000 −1
Data points n_points101
Shell type shell_typedirectional
Solvent electron density solvent_density0.3340 e/ų
Shell contrast contrast_shell0.0300 e/ų
CRYSOL version crysol_version4.1.3

4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

Maximum dimension Dmax dmax72.0
Rg (real space) rg_real20.52
Rg uncertainty (real space) rg_real_error0.45
I(0) (real space) i0_real1.9600e+07
I(0) uncertainty (real space) i0_real_error2.3940e+05
Rg (reciprocal space) rg_reciprocal20.54
I(0) (reciprocal space) i0_reciprocal19600000.0000
Solution quality estimate total_estimate0.7856
Solution quality rating solution_quality GOOD a GOOD solution
P(r) peaks n_peaks3
Primary peak position r_peak_primary24.0
Skewness Skewness skewness0.199
Kurtosis Kurtosis kurtosis-0.456
Angular range angular_range— – 0.3850 −1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha5892000.0000
Real-space data points n_real_points70
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.738; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.995; Smooth: 0.000

5. Crystallography and Experiment 5. Crystallography & Experiment

6. Entities and Polymers Entities & Polymers (3)

7. Fold Classification (SCOP + CATH) 3 domains

SCOP 2.08 (1 domains)

Domain ID domain_idd4ag8a_
Class classd — Alpha and beta proteins (a+b)
Fold Fold foldd.144 — Protein kinase-like (PK-like)
Superfamily Superfamily superfamilyd.144.1 — Protein kinase-like (PK-like)
Family Family familyd.144.1.7 — Protein kinases, catalytic subunit

CATH v4.4 (2 domains)

Domain ID domain_id4ag8A01
Class class3 — Alpha Beta
Architecture architecture30 — 2-Layer Sandwich
Topology topology200 — Phosphorylase Kinase; domain 1
Homologous superfamily homologous superfamily20 — Phosphorylase Kinase; domain 1
Domain ID domain_id4ag8A02
Class class1 — Mainly Alpha
Architecture architecture10 — Orthogonal Bundle
Topology topology510 — Transferase(Phosphotransferase); domain 1
Homologous superfamily homologous superfamily10 — Transferase(Phosphotransferase) domain 1

8. Citations (1)

9. Files and Curves (10)