8stg

Discovery and clinical validation of RLY-4008, the first highly selective FGFR2 inhibitor with activity across FGFR2 alterations and resistance mutations

Method: X-RAY DIFFRACTION Dmax: 89.5 Å Quality: EXCELLENT

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

Fibroblast growth factor receptor 2

Homo sapiens

UniProt P21802

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 458–769 Fragment:kinase domain (UNP residues 458-769) WCJ N-{4-[(5P)-4-amino-5-{3-fluoro-4-[(4-methylpyrimidin-2-yl)oxy]phenyl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl}-2-methylpropanamide × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION, HANGING DROP;pH 8;291.15 K;0.1 M Tris, pH 8, 18-20% w/v PEG8000 Resolution 3.79 Å R-free 0.311
2 Protein monomer Monomer Protein × 1 PDB declaration: monomeric(1) Consistent with protein copy count Chain B; UniProt 458–769 Fragment:kinase domain (UNP residues 458-769) WCJ N-{4-[(5P)-4-amino-5-{3-fluoro-4-[(4-methylpyrimidin-2-yl)oxy]phenyl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl}-2-methylpropanamide × 1 X-RAY DIFFRACTION X-ray crystallization conditions:VAPOR DIFFUSION, HANGING DROP;pH 8;291.15 K;0.1 M Tris, pH 8, 18-20% w/v PEG8000 Resolution 3.79 Å R-free 0.311

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.

60 other PDB entries and 122 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name FGFR2_HUMAN
Isoform
PDB entities 1
Chains and sequence ranges Author chain A; PDBConstruct 6–317; UniProt 458–769 Author chain B; PDBConstruct 6–317; UniProt 458–769

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 8stg

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 8stg
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2. Structure Basics 2. Structure Basics

Entry ID entry_id8stg
Deposition date deposition_date2023-05-10
Structure title titleDiscovery and clinical validation of RLY-4008, the first highly selective FGFR2 inhibitor with activity across FGFR2 alterations and resistance mutations
Keywords keywordsRelay Inhibitor, CYTOSOLIC PROTEIN, TRANSFERASE-INHIBITOR complex; TRANSFERASE/INHIBITOR
Experimental Method methodX-RAY DIFFRACTION

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

Radius of gyration Rg (Guinier) rg_guinier28.42
Radius of gyration Rg (electron density) rg_electron27.61
Forward intensity I(0) i064514700.00
Molecular weight molecular_weight63491.0 kDa
Excluded volume excluded_volume79859 ų
Envelope volume envelope_volume103960 ų
Hydration-shell volume shell_volume31450 ų
Envelope diameter envelope_diameter93.5
Shell Rg shell_rg34.82
Envelope Rg envelope_rg27.34
Shape Rg shape_rg27.59
Total Rg total_rg28.45
Total atoms total_atoms8888
Residues n_residues551
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 dmax89.5
Rg (real space) rg_real28.36
Rg uncertainty (real space) rg_real_error0.65
I(0) (real space) i0_real6.4510e+07
I(0) uncertainty (real space) i0_real_error9.6440e+05
Rg (reciprocal space) rg_reciprocal28.38
I(0) (reciprocal space) i0_reciprocal64520000.0000
Solution quality estimate total_estimate0.9051
Solution quality rating solution_quality EXCELLENT a EXCELLENT solution
P(r) peaks n_peaks2
Primary peak position r_peak_primary30.4
Skewness Skewness skewness0.226
Kurtosis Kurtosis kurtosis-0.571
Angular range angular_range— – 0.2800 −1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha33760000.0000
Real-space data points n_real_points57
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.946; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.992; Smooth: 0.931

5. Crystallography and Experiment 5. Crystallography & Experiment

6. Entities and Polymers Entities & Polymers (2)

7. Fold Classification (SCOP + CATH) 2 domains

CATH v4.4 (2 domains)

Domain ID domain_id8stgA01
Class class1 — Mainly Alpha
Architecture architecture10 — Orthogonal Bundle
Topology topology510 — Transferase(Phosphotransferase); domain 1
Homologous superfamily homologous superfamily10 — Transferase(Phosphotransferase) domain 1
Domain ID domain_id8stgB01
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)