5tbm

Crystal structure of PT2385 bound to HIF2a-B*:ARNT-B* complex

Method: X-RAY DIFFRACTION Dmax: 65.6 Å Quality: GOOD

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

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 237–348 Fragment:UNP residues 237-248 Aryl hydrocarbon receptor nuclear translocator × 1 (P27540) 79A 3-{[(1S)-2,2-difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl]oxy}-5-fluorobenzonitrile × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION;pH 5.4;293 K;50 mM Bis-Tris pH5.4, 16% PEG 3350. use freshly crushed crystal as seed. Resolution 1.85 Å R-free 0.300
2 Protein heterocomplex Heteromer Protein × 2 PDB declaration: dimeric(2) Consistent with protein copy count Chain A; UniProt 237–348 Fragment:UNP residues 237-248 Aryl hydrocarbon receptor nuclear translocator × 1 (P27540) 79A 3-{[(1S)-2,2-difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl]oxy}-5-fluorobenzonitrile × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION;pH 5.4;293 K;50 mM Bis-Tris pH5.4, 16% PEG 3350. use freshly crushed crystal as seed. Resolution 1.85 Å R-free 0.300

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 1
Chains and sequence ranges Author chain A; PDBConstruct 4–115; UniProt 237–348

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 340–453 Fragment:UNP residues 340-453 Endothelial PAS domain-containing protein 1 × 1 (Q99814) 79A 3-{[(1S)-2,2-difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl]oxy}-5-fluorobenzonitrile × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION;pH 5.4;293 K;50 mM Bis-Tris pH5.4, 16% PEG 3350. use freshly crushed crystal as seed. Resolution 1.85 Å R-free 0.300
2 Protein heterocomplex Heteromer Protein × 2 PDB declaration: dimeric(2) Consistent with protein copy count Chain B; UniProt 340–453 Fragment:UNP residues 340-453 Endothelial PAS domain-containing protein 1 × 1 (Q99814) 79A 3-{[(1S)-2,2-difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl]oxy}-5-fluorobenzonitrile × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION;pH 5.4;293 K;50 mM Bis-Tris pH5.4, 16% PEG 3350. use freshly crushed crystal as seed. Resolution 1.85 Å R-free 0.300

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 2
Chains and sequence ranges Author chain B; PDBConstruct 4–117; UniProt 340–453

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 5tbm

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 5tbm
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2. Structure Basics 2. Structure Basics

Entry ID entry_id5tbm
Deposition date deposition_date2016-09-12
Structure title titleCrystal structure of PT2385 bound to HIF2a-B*:ARNT-B* complex
Keywords keywordsHIF2 inhibitor HIF2 ligand PAS-B hypoxia inducible factor 2 EPAS1, TRANSCRIPTION; TRANSCRIPTION
Experimental Method methodX-RAY DIFFRACTION

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

Radius of gyration Rg (Guinier) rg_guinier19.29
Radius of gyration Rg (electron density) rg_electron18.53
Forward intensity I(0) i012191700.00
Molecular weight molecular_weight25632.0 kDa
Excluded volume excluded_volume31837 ų
Envelope volume envelope_volume37296 ų
Hydration-shell volume shell_volume17147 ų
Envelope diameter envelope_diameter70.6
Shell Rg shell_rg24.29
Envelope Rg envelope_rg19.05
Shape Rg shape_rg18.51
Total Rg total_rg19.46
Total atoms total_atoms1799
Residues n_residues216
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 dmax65.6
Rg (real space) rg_real19.26
Rg uncertainty (real space) rg_real_error0.54
I(0) (real space) i0_real1.2190e+07
I(0) uncertainty (real space) i0_real_error1.6100e+05
Rg (reciprocal space) rg_reciprocal19.27
I(0) (reciprocal space) i0_reciprocal12190000.0000
Solution quality estimate total_estimate0.7965
Solution quality rating solution_quality GOOD a GOOD solution
P(r) peaks n_peaks3
Primary peak position r_peak_primary22.2
Skewness Skewness skewness0.318
Kurtosis Kurtosis kurtosis-0.336
Angular range angular_range— – 0.4100 −1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha2892000.0000
Real-space data points n_real_points72
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.797; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.960; Smooth: 0.000

5. Crystallography and Experiment 5. Crystallography & Experiment

6. Entities and Polymers Entities & Polymers (4)

7. Fold Classification (SCOP + CATH) 4 domains

SCOP 2.08 (2 domains)

Domain ID domain_idd5tbma_
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_idd5tbmb_
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 (2 domains)

Domain ID domain_id5tbmA00
Class class3 — Alpha Beta
Architecture architecture30 — 2-Layer Sandwich
Topology topology450 — Beta-Lactamase
Homologous superfamily homologous superfamily20 — PAS domain
Domain ID domain_id5tbmB01
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)