← Back to search
4x3j

Selection of fragments for kinase inhibitor design: decoration is key

Method: X-RAY DIFFRACTION Dmax: 60.2 Å Quality: GOOD
▼

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

Angiopoietin-1 receptor

Homo sapiens

UniProt Q02763

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 802–1122 Fragment：Kinase domain, UNP residues 802-1122 Mutation：D964N 3WR 1-[4-(4-amino-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)phenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea × 1 X-RAY DIFFRACTION X-ray crystallization conditions：VAPOR DIFFUSION, HANGING DROP；pH 7；293 K；0.1 M Tris/HCl pH 7.0 0.05 M NaCl 0.03 M Lithiumsulfat Resolution 2.50 Å R-free 0.293

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.

Other PDB Difference from Current Entry 4X3J Assembly / Oligomeric State Construct Mutations and Modifications Ligands, Ions and Non-polymers Method and Experimental Conditions Structure Quality
1FVR TIE2 KINASE DOMAIN Deposited 2000-09-20 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 808–1124（317 aa） Fragment：KINASE DOMAIN
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 7.5；295 K；2.5% PEG12000, 2.5% glycerol, 100mM Hepes, 10mM spermidine, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 22K
Resolution 2.20 Å R-free 0.225
1FVR TIE2 KINASE DOMAIN Deposited 2000-09-20 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 808–1124（317 aa） Fragment：KINASE DOMAIN
Not recorded No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 7.5；295 K；2.5% PEG12000, 2.5% glycerol, 100mM Hepes, 10mM spermidine, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 22K
Resolution 2.20 Å R-free 0.225
2GY5 Tie2 Ligand-Binding Domain Crystal Structure Deposited 2006-05-09 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 23–445（423 aa） Fragment：Ligand-binding domain (residues 23-445)
Not recorded NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 1 NDG 2-acetamido-2-deoxy-alpha-D-glucopyranose × 4 SO4 SULFATE ION × 4 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6；293 K；2.2M Ammonium Sulfate, 0.1M MES, pH 6.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K
Resolution 2.90 Å R-free 0.294
2GY7 Angiopoietin-2/Tie2 Complex Crystal Structure Deposited 2006-05-09 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Other combination Heteromer；Protein × 2 PDB declaration: dimeric
Chain B 23–445（423 aa） Fragment：Tie2 Ligand-binding domain (residues 23-445)
Not recorded CA CALCIUM ION × 1 NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 1 SO4 SULFATE ION × 2 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 6；293 K；2.2 M Ammonium Sulfate, 0.1M MES, pH 6.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K
Resolution 3.70 Å R-free 0.317
2OO8 Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors Deposited 2007-01-25 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain X 808–1124（317 aa） Fragment：Kinase domain
Not recorded RAJ N-{3-[3-(DIMETHYLAMINO)PROPYL]-5-(TRIFLUOROMETHYL)PHENYL}-4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]BENZAMIDE × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 7；298 K；14-18 % (w/v) PEG 3350, and 0.2 M tri-Potassium Citrate (pH 6.5-7.5), and 2% (v/v) isopropanol, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K
Resolution 2.20 Å R-free 0.279
2OSC Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors Deposited 2007-02-05 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 808–1124（317 aa） Fragment：Tie-2 Kinase domain
Not recorded MUH N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 7；298 K；14-18 % (w/v) PEG 3350, and 0.2 M tri-Potassium Citrate (pH 6.5-7.5), and 2% (v/v) isopropanol, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K
Resolution 2.80 Å R-free 0.306
2P4I Evolution of a highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor Deposited 2007-03-12 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 808–1124（317 aa）
Not recorded MR9 4-METHYL-3-({3-[2-(METHYLAMINO)PYRIMIDIN-4-YL]PYRIDIN-2-YL}OXY)-N-[2-MORPHOLIN-4-YL-5-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 7；298 K；14-18% PEG 3350, 0.2M tri-Potassium Citrate (pH 6.5-7.5) and 2% isopropanol., pH 7.0, VAPOR DIFFUSION, temperature 298K
Resolution 2.50 Å R-free 0.303
2P4I Evolution of a highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor Deposited 2007-03-12 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 808–1124（317 aa）
Not recorded MR9 4-METHYL-3-({3-[2-(METHYLAMINO)PYRIMIDIN-4-YL]PYRIDIN-2-YL}OXY)-N-[2-MORPHOLIN-4-YL-5-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 7；298 K；14-18% PEG 3350, 0.2M tri-Potassium Citrate (pH 6.5-7.5) and 2% isopropanol., pH 7.0, VAPOR DIFFUSION, temperature 298K
Resolution 2.50 Å R-free 0.303
2WQB Structure of the Tie2 kinase domain in complex with a thiazolopyrimidine inhibitor Deposited 2009-08-18 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 802–1124（323 aa） Fragment：KINASE DOMAIN, RESIDUES 802-1124
Mutation：YES QQ1 2-[3-(CYCLOHEXYLMETHYL)-5-PHENYL-IMIDAZOL-4-YL]-[1,3]THIAZOLO[4,5-E]PYRIMIDIN-7-AMINE × 1 X-RAY DIFFRACTION
X-ray crystallization conditions pH 7.5；293 K；5 MG/ML PROTEIN, 5% (W/V) PEG6000, 5% (V/V) MPD, 100MM MOPS PH7.5, 293K
Resolution 2.95 Å R-free 0.259
3BEA cFMS tyrosine kinase (tie2 KID) in complex with a pyrimidinopyridone inhibitor Deposited 2007-11-16 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Insufficient information Monomer；Protein × 1 PDB declaration: monomeric
Chain A 917–935（19 aa）
Mutation：A695L SO4 SULFATE ION × 3 IXH 8-(2,3-dihydro-1H-inden-5-yl)-2-({4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]phenyl}amino)-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxamide × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 5.2；298 K；PEG 3350, sodium acetate, Li2SO4, pH 5.2, VAPOR DIFFUSION, HANGING DROP, temperature 298K
Resolution 2.02 Å R-free 0.230
3L8P Crystal structure of cytoplasmic kinase domain of Tie2 complexed with inhibitor CEP11207 Deposited 2010-01-03 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 808–1124（317 aa） Fragment：Tie2 fragment 808-1124
Not recorded 0CE 2-methyl-11-(1-methylethyl)-8-[(2S)-tetrahydro-2H-pyran-2-yl]-2,11,12,13-tetrahydro-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 7；277 K；8% PEG 3350, 0.2M Tri-Ammonium Citrate, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 277.0K
Resolution 2.40 Å R-free 0.265
5MYA Homodimerization of Tie2 Fibronectin-like domains 1-3 in space group C2 Deposited 2017-01-26 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Other combination Homooligomer；Protein × 2 PDB declaration: dimeric
Chain A 443–742（300 aa）
Chain B 443–742（300 aa）
Not recorded NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 4 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；294 K；0.1 M Tris buffer at pH 7.0 - 8.5 and 14-20% PEG 3350 (w/v)
Resolution 2.90 Å R-free 0.277
5MYB Homodimerization of Tie2 Fibronectin-like domains 2 and 3 in space group P21 Deposited 2017-01-26 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Other combination Homooligomer；Protein × 2 PDB declaration: dimeric
Chain A 443–742（300 aa）
Chain B 443–742（300 aa）
Not recorded NAG 2-acetamido-2-deoxy-beta-D-glucopyranose × 4 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；294 K；0.1 M Tris buffer at pH 7.0 - 8.5 and 14-20% PEG 3350 (w/v)
Resolution 2.60 Å R-free 0.278
5UTK Crystal structure of the membrane proximal three fibronectin type III (FNIII) domains of Tie2 (Tie2[FNIIIa-c]) Deposited 2017-02-15 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric
Chain A 399–698（300 aa） Fragment：unp residues 399-698
Chain B 399–698（300 aa） Fragment：unp residues 399-698
Non-standard monomer：Yes (specific site not provided by mmCIF) Non-standard monomer：Yes (specific site not provided by mmCIF) No recorded non-water small molecule X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 4.5；277 K；25-40% glycerol, 2.5-15% PEG 3K, 100 mM sodium acetate, 100 mM sodium phosphate, pH 4.5
Resolution 2.50 Å R-free 0.247
6MWE CRYSTAL STRUCTURE OF TIE2 IN COMPLEX WITH DECIPERA COMPOUND DP1919 Deposited 2018-10-29 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 808–1124（317 aa）
Not recorded SO4 SULFATE ION × 2 919 4-[4-({[3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 4.6；290 K；JCSG+ screen e4: 1.26M ammonium sulphate: 200mM lithium sulphate, 100mM Tris pH 8.5: cryo: 25% EG in 3 steps
Resolution 2.05 Å R-free 0.166
6MWE CRYSTAL STRUCTURE OF TIE2 IN COMPLEX WITH DECIPERA COMPOUND DP1919 Deposited 2018-10-29 Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain B 808–1124（317 aa）
Not recorded SO4 SULFATE ION × 2 919 4-[4-({[3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 4.6；290 K；JCSG+ screen e4: 1.26M ammonium sulphate: 200mM lithium sulphate, 100mM Tris pH 8.5: cryo: 25% EG in 3 steps
Resolution 2.05 Å R-free 0.166
7E72 Crystal structure of Tie2-agonistic antibody in complex with human Tie2 Fn2-3 Deposited 2021-02-25 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein heterocomplex Heteromer；Protein × 3 PDB declaration: trimeric
Chain E 541–735（195 aa）
Not recorded EDO 1,2-ETHANEDIOL × 22 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 8.5；292.15 K；100 mM Bis-Tris propane pH 8.5, 110 mM potassium dihydrogen phosphate, 15% (w/v) polyethylene glycol 3350
Resolution 2.09 Å R-free 0.233
7E72 Crystal structure of Tie2-agonistic antibody in complex with human Tie2 Fn2-3 Deposited 2021-02-25 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 2 Protein heterocomplex Heteromer；Protein × 3 PDB declaration: trimeric
Chain F 541–735（195 aa）
Not recorded EDO 1,2-ETHANEDIOL × 12 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 8.5；292.15 K；100 mM Bis-Tris propane pH 8.5, 110 mM potassium dihydrogen phosphate, 15% (w/v) polyethylene glycol 3350
Resolution 2.09 Å R-free 0.233
9LV4 Cryo-EM Structure of Human Tie2/minibinder tw1102_4 helices Complex Deposited 2025-02-11 Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric
Chain B 23–452（430 aa）
Not recorded No recorded non-water small molecule ELECTRON MICROSCOPY
cryo-EM buffer pH 8
cryo-EM vitrification conditions Cryogen ETHANE；blot for 3 seconds before plunging
Resolution 2.67 Å

15 other PDB entries and 19 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name TIE2_HUMAN
Isoform —
PDB entities 1
Chains and sequence ranges Author chain A； PDBConstruct 1–321； UniProt 802–1122

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 4x3j

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 4x3j
Download Download
▼

2. Structure Basics 2. Structure Basics

Entry ID entry_id4x3j
Deposition date deposition_date2014-11-30
Structure title titleSelection of fragments for kinase inhibitor design: decoration is key
Keywords keywordsTRANSFERASE, PROTEIN KINASE, INHIBITOR COMPLEX; TRANSFERASE
Experimental Method methodX-RAY DIFFRACTION
▼

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

Radius of gyration Rg (Guinier) rg_guinier18.92 Å
Radius of gyration Rg (electron density) rg_electron17.96 Å
Forward intensity I(0) i012686200.00
Molecular weight molecular_weight27240.0 kDa
Excluded volume excluded_volume34316 ų
Envelope volume envelope_volume39909 ų
Hydration-shell volume shell_volume18455 ų
Envelope diameter envelope_diameter64.7 Å
Shell Rg shell_rg24.40 Å
Envelope Rg envelope_rg18.50 Å
Shape Rg shape_rg17.94 Å
Total Rg total_rg19.01 Å
Total atoms total_atoms1919
Residues n_residues234
Spherical-harmonic order n_harmonics20
q range q_range— – 0.5000 Å−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 dmax60.2 Å
Rg (real space) rg_real18.81 Å
Rg uncertainty (real space) rg_real_error0.37 Å
I(0) (real space) i0_real1.2690e+07
I(0) uncertainty (real space) i0_real_error1.6450e+05
Rg (reciprocal space) rg_reciprocal18.83 Å
I(0) (reciprocal space) i0_reciprocal12690000.0000
Solution quality estimate total_estimate0.8157
Solution quality rating solution_quality GOOD a GOOD solution
P(r) peaks n_peaks3
Primary peak position r_peak_primary24.3 Å
Skewness Skewness skewness0.177
Kurtosis Kurtosis kurtosis-0.414
Angular range angular_range— – 0.4200 Å−1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha3938000.0000
Real-space data points n_real_points73
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.868; Stabil: 0.999; Sysdev: 1.000; Positv: 1.000; Valcen: 0.999; 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_idd4x3ja_
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_id4x3jA01
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_id4x3jA02
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)