[English] 日本語
Yorodumi
- PDB-8ff0: Structure of BTK kinase domain with the second-generation inhibit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8ff0
TitleStructure of BTK kinase domain with the second-generation inhibitor tirabrutinib
ComponentsTyrosine-protein kinase BTK
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / inhibitor / kinase / complex / covalent / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


negative regulation of B cell activation / G beta:gamma signalling through BTK / RHO GTPases Activate WASPs and WAVEs / FCERI mediated Ca+2 mobilization / G alpha (q) signalling events / G alpha (12/13) signalling events / negative regulation of leukocyte proliferation / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of actin dynamics for phagocytic cup formation / proteoglycan catabolic process ...negative regulation of B cell activation / G beta:gamma signalling through BTK / RHO GTPases Activate WASPs and WAVEs / FCERI mediated Ca+2 mobilization / G alpha (q) signalling events / G alpha (12/13) signalling events / negative regulation of leukocyte proliferation / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of actin dynamics for phagocytic cup formation / proteoglycan catabolic process / monocyte proliferation / positive regulation of interleukin-17A production / eosinophil homeostasis / positive regulation of type III hypersensitivity / B cell affinity maturation / positive regulation of synoviocyte proliferation / histamine secretion by mast cell / neutrophil homeostasis / cellular response to molecule of fungal origin / positive regulation of type I hypersensitivity / cellular response to interleukin-7 / negative regulation of cytokine production / DAP12 signaling / positive regulation of immunoglobulin production / positive regulation of NLRP3 inflammasome complex assembly / negative regulation of interleukin-10 production / phospholipase activator activity / negative regulation of B cell proliferation / phosphatidylinositol-3,4,5-trisphosphate binding / phospholipase binding / positive regulation of phagocytosis / positive regulation of B cell proliferation / cell maturation / : / B cell receptor signaling pathway / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / cellular response to reactive oxygen species / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / T cell receptor signaling pathway / cytoplasmic vesicle / protein tyrosine kinase activity / adaptive immune response / response to lipopolysaccharide / intracellular signal transduction / membrane raft / phosphorylation / innate immune response / apoptotic process / perinuclear region of cytoplasm / ATP binding / identical protein binding / metal ion binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Tyrosine-protein kinase BTK, SH3 domain / Zinc finger, Btk motif / BTK motif / Zinc finger Btk-type profile. / Bruton's tyrosine kinase Cys-rich motif / PH domain / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / SH3 domain ...Tyrosine-protein kinase BTK, SH3 domain / Zinc finger, Btk motif / BTK motif / Zinc finger Btk-type profile. / Bruton's tyrosine kinase Cys-rich motif / PH domain / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / PH-like domain superfamily / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Chem-7GB / Tyrosine-protein kinase BTK
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsLin, D.Y. / Andreotti, A.H.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: Plos One / Year: 2023
Title: Structure of BTK kinase domain with the second-generation inhibitors acalabrutinib and tirabrutinib.
Authors: Lin, D.Y. / Andreotti, A.H.
History
DepositionDec 7, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 5, 2023Provider: repository / Type: Initial release
Revision 1.1Sep 13, 2023Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / citation
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tyrosine-protein kinase BTK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2782
Polymers31,8221
Non-polymers4561
Water1086
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)108.187, 108.187, 45.172
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number169
Space group name H-MP61
Space group name HallP61
Symmetry operation#1: x,y,z
#2: x-y,x,z+1/6
#3: y,-x+y,z+5/6
#4: -y,x-y,z+1/3
#5: -x+y,-x,z+2/3
#6: -x,-y,z+1/2

-
Components

#1: Protein Tyrosine-protein kinase BTK / Agammaglobulinemia tyrosine kinase / ATK / B-cell progenitor kinase / BPK / Bruton tyrosine kinase ...Agammaglobulinemia tyrosine kinase / ATK / B-cell progenitor kinase / BPK / Bruton tyrosine kinase / Kinase EMB


Mass: 31821.521 Da / Num. of mol.: 1
Mutation: K430R, L542M S543T, V555T, R562K, S564A, P565S, Y617P
Source method: isolated from a genetically manipulated source
Details: Bruton's Tyrosine Kinase in complex with tirabrutinib
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Btk, Bpk / Production host: Escherichia coli (E. coli)
References: UniProt: P35991, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-7GB / 6-azanyl-9-[(3~{R})-1-[(~{E})-but-2-enoyl]pyrrolidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one


Mass: 456.496 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H24N6O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.32 Å3/Da / Density % sol: 48.73 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5.5 / Details: 16% PEG 8000 and 0.1M sodium citrate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97918 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Jul 7, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 2.6→19.41 Å / Num. obs: 8801 / % possible obs: 93.5 % / Redundancy: 9.9 % / Biso Wilson estimate: 93.78 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.064 / Rpim(I) all: 0.022 / Rrim(I) all: 0.068 / Net I/σ(I): 17.2
Reflection shellResolution: 2.603→2.705 Å / Redundancy: 9.9 % / Mean I/σ(I) obs: 1.1 / Num. unique obs: 440 / CC1/2: 0.455 / Rpim(I) all: 0.685 / % possible all: 44

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
autoPROCdata processing
PHASERphasing
autoPROCdata scaling
Cootmodel building
autoPROCdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.6→19.41 Å / SU ML: 0.2797 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 36.69
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2667 399 4.54 %
Rwork0.241 8399 -
obs0.2423 8798 93.46 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 100.76 Å2
Refinement stepCycle: LAST / Resolution: 2.6→19.41 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2047 0 34 6 2087
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00312131
X-RAY DIFFRACTIONf_angle_d0.80472891
X-RAY DIFFRACTIONf_chiral_restr0.0482314
X-RAY DIFFRACTIONf_plane_restr0.0052367
X-RAY DIFFRACTIONf_dihedral_angle_d15.4117758
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.6-2.980.35951040.35632368X-RAY DIFFRACTION80.13
2.98-3.750.33631470.31332985X-RAY DIFFRACTION100
3.75-19.410.23951480.20933046X-RAY DIFFRACTION99.91
Refinement TLS params.Method: refined / Origin x: 35.0008846426 Å / Origin y: -20.892153539 Å / Origin z: -2.25120645917 Å
111213212223313233
T0.795542696466 Å20.0324177594052 Å2-0.0839019817281 Å2-0.705080781164 Å2-0.0757078667333 Å2--0.696295300742 Å2
L1.78681475311 °20.90821556603 °20.91098967042 °2-4.94226374805 °21.96598709768 °2--2.45546928006 °2
S-0.33716333364 Å °0.00888135168986 Å °0.337536054391 Å °-0.284579623872 Å °-0.164536032616 Å °0.239072370769 Å °-0.473854077269 Å °-0.0626905022388 Å °-0.000361508146532 Å °
Refinement TLS groupSelection details: all

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more