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8fd9

Structure of BTK kinase domain with the second-generation inhibitor acalabrutinib

Method: X-RAY DIFFRACTION Dmax: 76.7 Å Quality: REASONABLE
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1. Protein Identity and Related Structures Protein Identity & Related Structures

Tyrosine-protein kinase BTK

Mus musculus

UniProt P35991

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 396–659 Mutation：K430R, L542M S543T, V555T, R562K, S564A, P565S, Y617P XQQ 4-[(4S)-8-amino-3-{(2S)-1-[(2E)-but-2-enoyl]pyrrolidin-2-yl}imidazo[1,5-a]pyrazin-1-yl]-N-(pyridin-2-yl)benzamide × 1 BR BROMIDE ION × 4 X-RAY DIFFRACTION X-ray crystallization conditions：EVAPORATION；pH 6.5；277 K；20% PEG 3350, 0.1M Bis-tris propane, pH 6.5 and 0.2M sodium bromide Resolution 1.70 Å R-free 0.228

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 8FD9 Assembly / Oligomeric State Construct Mutations and Modifications Ligands, Ions and Non-polymers Method and Experimental Conditions Structure Quality
4XI2 Crystal Structure of an auto-inhibited form of Bruton's Tryrosine Kinase Deposited 2015-01-06 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 214–659（446 aa） Fragment：UNP residues 214-659
Not recorded AU GOLD ION × 4 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 8.5；277 K；Mix purified dimer protein at 5 mg/ml in 25 mM TRIS.Cl, pH 8.5, 10 mM NaCl, 5 mM DTT with an equal volume of the precipitant solution, 100 mM TRIS.Cl, pH 8.5, 200 mM Na.acetate, 7.5 % PEG 4,000, then suspend over 1 ml of precipitant solution. Wedge shaped crystals grew to approximately 0.1 mm on a side after a period of two weeks. Crystals were frozen by first transferring them, in four sequential steps, to a solution of 100 mM TRIS.Cl, pH 8.5, 200 mM Na.acetate, 15 % PEG 4,000. This was followed by transfer in six sequential steps to a solution containing 100 mM TRIS.Cl, pH 8.5, 200 mM Na.acetate, 15 % PEG 4,000, 30% glucose
Resolution 2.60 Å R-free 0.248
8FF0 Structure of BTK kinase domain with the second-generation inhibitor tirabrutinib Deposited 2022-12-07 Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain A 396–659（264 aa）
Mutation：K430R, L542M S543T, V555T, R562K, S564A, P565S, Y617P 7GB 6-azanyl-9-[(3~{R})-1-[(~{E})-but-2-enoyl]pyrrolidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 5.5；277 K；16% PEG 8000 and 0.1M sodium citrate
Resolution 2.60 Å R-free 0.267
8GMB Crystal structure of the full-length Bruton's tyrosine kinase (PH-TH domain not visible) Deposited 2023-03-24 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 1–659（659 aa）
Mutation：E298A, K300A, E301A, A384P, S386P, T387P, A388P, L390F, K430R, L542M S543T, V555T, R562K, S564A, P565S, Y617P 9AJ 2-[3'-(hydroxymethyl)-1-methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo[1,6-dihydro[3,4'-bipyridine]]-2'-yl]-7,7-dimethyl-3,4,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one × 2 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 7.5；277.15 K；20% PEG 3350, 0.1M Bis-Tris Propane, 0.2M potassium thiocyanate
Resolution 3.40 Å R-free 0.289
8S93 Crystal structure of the PH-TH/kinase complex of Bruton's tyrosine kinase Deposited 2023-03-27 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 1–171（171 aa） Fragment：PHTH domain residues 1-171 and Kinase domain residues 396-659
Chain A 396–659（264 aa） Fragment：PHTH domain residues 1-171 and Kinase domain residues 396-659
Mutation：Q91A, I92A, I94A, I95A, K430R, L542M S543T, V555T, R562K, S564A, P565S, Y617P Mutation：Q91A, I92A, I94A, I95A, K430R, L542M S543T, V555T, R562K, S564A, P565S, Y617P 9AJ 2-[3'-(hydroxymethyl)-1-methyl-5-({5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo[1,6-dihydro[3,4'-bipyridine]]-2'-yl]-7,7-dimethyl-3,4,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one × 1 ZN ZINC ION × 1 GOL GLYCEROL × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION；pH 5.6；277 K；20%PEG3350, 0.1M Bis-Tris, pH5.6, 0.2M magnesium chloride
Resolution 2.10 Å R-free 0.246
8S9F Crystal structure of the kinase domain of Bruton's Tyrosine Kinase bound to dasatinib Deposited 2023-03-28 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 382–659（278 aa）
Chain B 382–659（278 aa）
Mutation：L390G, Y551E, Y617P Mutation：L390G, Y551E, Y617P 1N1 N-(2-CHLORO-6-METHYLPHENYL)-2-({6-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]-2-METHYLPYRIMIDIN-4-YL}AMINO)-1,3-THIAZOLE-5-CARBOXAMIDE × 2 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7.5；277 K；42% PEG200, 0.1M HEPES
Resolution 2.60 Å R-free 0.284
9EJJ Bruton's tyrosine kinase in complex with compound PTI55 Deposited 2024-11-28 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 382–659（278 aa）
Mutation：L390G, Y551E, Y617P A1BIZ 4-{4-amino-1-[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N-[4-(trifluoromethoxy)pyridin-2-yl]benzamide × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；277 K；0.1M NaCitrate pH 5.5, 18% PEG3350
Resolution 2.03 Å R-free 0.242
9EJJ Bruton's tyrosine kinase in complex with compound PTI55 Deposited 2024-11-28 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 382–659（278 aa）
Mutation：L390G, Y551E, Y617P A1BIZ 4-{4-amino-1-[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N-[4-(trifluoromethoxy)pyridin-2-yl]benzamide × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；277 K；0.1M NaCitrate pH 5.5, 18% PEG3350
Resolution 2.03 Å R-free 0.242
9EJR Bruton's tyrosine kinase in complex with compound PTI52 Deposited 2024-11-28 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 382–659（278 aa）
Mutation：L390G, Y551E, Y617P A1BI0 4-{4-amino-1-[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N-(4-cyclopropylpyridin-2-yl)benzamide × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；277 K；0.1M NaCitrate pH 5.5, 18% PEG3350
Resolution 2.10 Å R-free 0.295
9EJR Bruton's tyrosine kinase in complex with compound PTI52 Deposited 2024-11-28 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 382–659（278 aa）
Mutation：L390G, Y551E, Y617P A1BI0 4-{4-amino-1-[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N-(4-cyclopropylpyridin-2-yl)benzamide × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；277 K；0.1M NaCitrate pH 5.5, 18% PEG3350
Resolution 2.10 Å R-free 0.295
9EJS Bruton's tyrosine kinase with mutations in the activation loop in complex with compound PTI52 Deposited 2024-11-28 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 396–659（264 aa）
Mutation：K430R, L542M, S543T, V555T, R562K, S564A, P565S A1BI0 4-{4-amino-1-[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N-(4-cyclopropylpyridin-2-yl)benzamide × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；277 K；Sodium citrate tribasic dihydrate pH 5.5, 16% w/v Polyethylene glycol 8,000
Resolution 2.26 Å R-free 0.246
9EJS Bruton's tyrosine kinase with mutations in the activation loop in complex with compound PTI52 Deposited 2024-11-28 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 396–659（264 aa）
Mutation：K430R, L542M, S543T, V555T, R562K, S564A, P565S A1BI0 4-{4-amino-1-[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N-(4-cyclopropylpyridin-2-yl)benzamide × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；277 K；Sodium citrate tribasic dihydrate pH 5.5, 16% w/v Polyethylene glycol 8,000
Resolution 2.26 Å R-free 0.246
9EJS Bruton's tyrosine kinase with mutations in the activation loop in complex with compound PTI52 Deposited 2024-11-28 Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics Assembly 3 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric
Chain C 396–659（264 aa）
Mutation：K430R, L542M, S543T, V555T, R562K, S564A, P565S A1BI0 4-{4-amino-1-[(3R)-1-(cyclopropanecarbonyl)piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N-(4-cyclopropylpyridin-2-yl)benzamide × 1 DMS DIMETHYL SULFOXIDE × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；277 K；Sodium citrate tribasic dihydrate pH 5.5, 16% w/v Polyethylene glycol 8,000
Resolution 2.26 Å R-free 0.246
9EJX Bruton's tyrosine kinase with mutations in the activation loop in complex with compound PTI42 Deposited 2024-11-29 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 396–659（264 aa）
Mutation：K430R, L542M, S543T, V555T, R562K, S564A, P565S,Y617P A1BI1 {(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl}(cyclopropyl)methanone × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；277 K；0.1 M Sodium citrate tribasic dihydrate pH 5.5, 18% w/v Polyethylene glycol 8,000
Resolution 2.86 Å R-free 0.296
9ME2 Bruton's tyrosine kinase with mutations in the activation loop in complex with compound A110162 Deposited 2024-12-05 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 396–659（264 aa）
Mutation：K430R, L542M, S543T, V555T, R562K, S564A, P565S,Y617P A1BKW 3-(4-phenoxyphenyl)-1-[(3S)-piperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；277 K；0.1 M Sodium citrate tribasic dihydrate pH 5.5, 18% w/v Polyethylene glycol 8,000
Resolution 3.38 Å R-free 0.286
9ME3 Bruton's tyrosine kinase with mutations in the activation loop in complex with compound P301390 Deposited 2024-12-06 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 396–659（264 aa）
Mutation：K430R, L542M, S543T, V555T, R562K, S564A, P565S,Y617P A1BJE 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；277 K；0.1 M Sodium citrate tribasic dihydrate pH 5.5, 18% w/v Polyethylene glycol 8,000
Resolution 3.05 Å R-free 0.288
9ZLJ Crystal structure of BTK kinase domain bound to compound YS1 Deposited 2025-12-08 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 382–659（278 aa）
Mutation：Y617P A1C20 N-{(1r,4r)-4-[2-(4-chlorophenoxy)acetamido]cyclohexyl}-N-[2-(4-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)ethyl]propanamide × 1 IMD IMIDAZOLE × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7；277 K；15-25% PEG3350, 0.1M imidazole
Resolution 1.60 Å R-free 0.218
9ZLM Crystal structure of BTK kinase domain bound to compound YS2 Deposited 2025-12-08 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 382–659（278 aa）
Mutation：Y617P A1C2Z N-[4-(3-{2-oxo-2-[3-(phenoxymethyl)azetidin-1-yl]acetamido}phenyl)oxan-4-yl]propanamide × 1 IMD IMIDAZOLE × 1 X-RAY DIFFRACTION
X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 7；277 K；15-25% PEG3350, 0.1M imidazole
Resolution 1.27 Å R-free 0.212

13 other PDB entries and 17 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name BTK_MOUSE
Isoform —
PDB entities 1
Chains and sequence ranges Author chain A； PDBConstruct 2–265； UniProt 396–659

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 8fd9

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 8fd9
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2. Structure Basics 2. Structure Basics

Entry ID entry_id8fd9
Deposition date deposition_date2022-12-02
Structure title titleStructure of BTK kinase domain with the second-generation inhibitor acalabrutinib
Keywords keywordsinhibitor, kinase, complex, covalent, TRANSFERASE-TRANSFERASE INHIBITOR complex; TRANSFERASE/TRANSFERASE INHIBITOR
Experimental Method methodX-RAY DIFFRACTION
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3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier20.51 Å
Radius of gyration Rg (electron density) rg_electron19.25 Å
Forward intensity I(0) i019053000.00
Molecular weight molecular_weight32366.0 kDa
Excluded volume excluded_volume40119 ų
Envelope volume envelope_volume46552 ų
Hydration-shell volume shell_volume20203 ų
Envelope diameter envelope_diameter74.8 Å
Shell Rg shell_rg25.79 Å
Envelope Rg envelope_rg19.71 Å
Shape Rg shape_rg19.25 Å
Total Rg total_rg20.15 Å
Total atoms total_atoms4428
Residues n_residues271
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
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4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

Maximum dimension Dmax dmax76.7 Å
Rg (real space) rg_real20.45 Å
Rg uncertainty (real space) rg_real_error0.61 Å
I(0) (real space) i0_real1.9050e+07
I(0) uncertainty (real space) i0_real_error2.4710e+05
Rg (reciprocal space) rg_reciprocal20.46 Å
I(0) (reciprocal space) i0_reciprocal19050000.0000
Solution quality estimate total_estimate0.5897
Solution quality rating solution_quality REASONABLE a REASONABLE solution
P(r) peaks n_peaks3
Primary peak position r_peak_primary25.2 Å
Skewness Skewness skewness0.318
Kurtosis Kurtosis kurtosis-0.199
Angular range angular_range— – 0.3900 Å−1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha6713000.0000
Real-space data points n_real_points71
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.586; Stabil: 1.000; Sysdev: 0.319; Positv: 1.000; Valcen: 0.947; Smooth: 0.000
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5. Crystallography and Experiment 5. Crystallography & Experiment

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6. Entities and Polymers Entities & Polymers (4)

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7. Fold Classification (SCOP + CATH) 2 domains

CATH v4.4 (2 domains)

Domain ID domain_id8fd9A01
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_id8fd9A02
Class class1 — Mainly Alpha
Architecture architecture10 — Orthogonal Bundle
Topology topology510 — Transferase(Phosphotransferase); domain 1
Homologous superfamily homologous superfamily10 — Transferase(Phosphotransferase) domain 1
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8. Citations (1)

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9. Files and Curves (10)