4xt2

Crystal structure of the high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains in complex with a tetrazole-containing antagonist

Method: X-RAY DIFFRACTION Dmax: 88.0 Å Quality: GOOD

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

Aryl hydrocarbon receptor nuclear translocator

Homo sapiens

UniProt P27540

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 heterocomplex Heteromer Protein × 2 PDB declaration: dimeric(2) Consistent with protein copy count Chain B; UniProt 342–456 Fragment:C-terminal PAS domain (UNP residues 342-456) Mutation:E362R Endothelial PAS domain-containing protein 1 × 1 (Q99814) 43L (5S,7R)-5,7-bis(3-bromophenyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION, HANGING DROP;pH 6.5;293.15 K;2 uL 500 uM protein against 100 mM Bis-Tris, 25% PEG3350 Resolution 1.70 Å R-free 0.192
2 Protein heterocomplex Heteromer Protein × 2 PDB declaration: dimeric(2) Consistent with protein copy count Chain D; UniProt 342–456 Fragment:C-terminal PAS domain (UNP residues 342-456) Mutation:E362R Endothelial PAS domain-containing protein 1 × 1 (Q99814) 43L (5S,7R)-5,7-bis(3-bromophenyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION, HANGING DROP;pH 6.5;293.15 K;2 uL 500 uM protein against 100 mM Bis-Tris, 25% PEG3350 Resolution 1.70 Å R-free 0.192

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.

42 other PDB entries and 47 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name ARNT_HUMAN
Isoform P27540-3
PDB entities 1
Chains and sequence ranges Author chain B; PDBConstruct 7–121; UniProt 342–456 Author chain D; PDBConstruct 7–121; UniProt 342–456

Endothelial PAS domain-containing protein 1

Homo sapiens

UniProt Q99814

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 heterocomplex Heteromer Protein × 2 PDB declaration: dimeric(2) Consistent with protein copy count Chain A; UniProt 239–350 Fragment:C-terminal PAS domain (UNP residues 239-350) Mutation:R247E Aryl hydrocarbon receptor nuclear translocator × 1 (P27540) 43L (5S,7R)-5,7-bis(3-bromophenyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION, HANGING DROP;pH 6.5;293.15 K;2 uL 500 uM protein against 100 mM Bis-Tris, 25% PEG3350 Resolution 1.70 Å R-free 0.192
2 Protein heterocomplex Heteromer Protein × 2 PDB declaration: dimeric(2) Consistent with protein copy count Chain C; UniProt 239–350 Fragment:C-terminal PAS domain (UNP residues 239-350) Mutation:R247E Aryl hydrocarbon receptor nuclear translocator × 1 (P27540) 43L (5S,7R)-5,7-bis(3-bromophenyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION, HANGING DROP;pH 6.5;293.15 K;2 uL 500 uM protein against 100 mM Bis-Tris, 25% PEG3350 Resolution 1.70 Å R-free 0.192

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.

41 other PDB entries and 45 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name EPAS1_HUMAN
Isoform
PDB entities 2
Chains and sequence ranges Author chain A; PDBConstruct 6–117; UniProt 239–350 Author chain C; PDBConstruct 6–117; UniProt 239–350

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 4xt2

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 4xt2
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2. Structure Basics 2. Structure Basics

Entry ID entry_id4xt2
Deposition date deposition_date2015-01-22
Structure title titleCrystal structure of the high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains in complex with a tetrazole-containing antagonist
Keywords keywordstranscription factor, Hypoxia Inducible Factor, inhibitor, cancer, TRANSCRIPTION; TRANSCRIPTION
Experimental Method methodX-RAY DIFFRACTION

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

Radius of gyration Rg (Guinier) rg_guinier25.99
Radius of gyration Rg (electron density) rg_electron25.60
Forward intensity I(0) i048920300.00
Molecular weight molecular_weight53272.0 kDa
Excluded volume excluded_volume66019 ų
Envelope volume envelope_volume78892 ų
Hydration-shell volume shell_volume26705 ų
Envelope diameter envelope_diameter91.0
Shell Rg shell_rg31.84
Envelope Rg envelope_rg25.61
Shape Rg shape_rg25.65
Total Rg total_rg26.11
Total atoms total_atoms7320
Residues n_residues448
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 dmax88.0
Rg (real space) rg_real26.04
Rg uncertainty (real space) rg_real_error0.86
I(0) (real space) i0_real4.8920e+07
I(0) uncertainty (real space) i0_real_error8.2140e+05
Rg (reciprocal space) rg_reciprocal26.03
I(0) (reciprocal space) i0_reciprocal48920000.0000
Solution quality estimate total_estimate0.8776
Solution quality rating solution_quality GOOD a GOOD solution
P(r) peaks n_peaks3
Primary peak position r_peak_primary26.0
Skewness Skewness skewness0.390
Kurtosis Kurtosis kurtosis-0.387
Angular range angular_range— – 0.3050 −1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha16640000.0000
Real-space data points n_real_points62
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.833; Stabil: 0.998; Sysdev: 1.000; Positv: 1.000; Valcen: 0.927; Smooth: 0.984

5. Crystallography and Experiment 5. Crystallography & Experiment

6. Entities and Polymers Entities & Polymers (4)

7. Fold Classification (SCOP + CATH) 10 domains

SCOP 2.08 (6 domains)

Domain ID domain_idd4xt2a1
Class classd — Alpha and beta proteins (a+b)
Fold Fold foldd.110 — Profilin-like
Superfamily Superfamily superfamilyd.110.3 — PYP-like sensor domain (PAS domain)
Family Family familyd.110.3.7 — Hypoxia-inducible factor Hif2a, C-terminal domain
Domain ID domain_idd4xt2a2
Class classl — Artifacts
Fold Fold foldl.1 — Tags
Superfamily Superfamily superfamilyl.1.1 — Tags
Family Family familyl.1.1.1 — Tags
Domain ID domain_idd4xt2b_
Class classd — Alpha and beta proteins (a+b)
Fold Fold foldd.110 — Profilin-like
Superfamily Superfamily superfamilyd.110.3 — PYP-like sensor domain (PAS domain)
Family Family familyd.110.3.0 — automated matches
Domain ID domain_idd4xt2c1
Class classd — Alpha and beta proteins (a+b)
Fold Fold foldd.110 — Profilin-like
Superfamily Superfamily superfamilyd.110.3 — PYP-like sensor domain (PAS domain)
Family Family familyd.110.3.7 — Hypoxia-inducible factor Hif2a, C-terminal domain
Domain ID domain_idd4xt2c2
Class classl — Artifacts
Fold Fold foldl.1 — Tags
Superfamily Superfamily superfamilyl.1.1 — Tags
Family Family familyl.1.1.1 — Tags
Domain ID domain_idd4xt2d_
Class classd — Alpha and beta proteins (a+b)
Fold Fold foldd.110 — Profilin-like
Superfamily Superfamily superfamilyd.110.3 — PYP-like sensor domain (PAS domain)
Family Family familyd.110.3.0 — automated matches

CATH v4.4 (4 domains)

Domain ID domain_id4xt2A00
Class class3 — Alpha Beta
Architecture architecture30 — 2-Layer Sandwich
Topology topology450 — Beta-Lactamase
Homologous superfamily homologous superfamily20 — PAS domain
Domain ID domain_id4xt2B01
Class class3 — Alpha Beta
Architecture architecture30 — 2-Layer Sandwich
Topology topology450 — Beta-Lactamase
Homologous superfamily homologous superfamily20 — PAS domain
Domain ID domain_id4xt2C00
Class class3 — Alpha Beta
Architecture architecture30 — 2-Layer Sandwich
Topology topology450 — Beta-Lactamase
Homologous superfamily homologous superfamily20 — PAS domain
Domain ID domain_id4xt2D01
Class class3 — Alpha Beta
Architecture architecture30 — 2-Layer Sandwich
Topology topology450 — Beta-Lactamase
Homologous superfamily homologous superfamily20 — PAS domain

8. Citations (1)

9. Files and Curves (10)