[English] 日本語
Yorodumi
- PDB-5vfi: Bruton's tyrosine kinase (BTK) with GDC-0853 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5vfi
TitleBruton's tyrosine kinase (BTK) with GDC-0853
ComponentsTyrosine-protein kinase BTK
KeywordsTransferase/Transferase Inhibitor / protein kinase inhibitor / Transferase-Transferase Inhibitor complex
Function / homology
Function and homology information


regulation of B cell cytokine production / regulation of B cell apoptotic process / monocyte proliferation / positive regulation of interleukin-17A production / proteoglycan catabolic process / eosinophil homeostasis / positive regulation of type III hypersensitivity / negative regulation of B cell activation / positive regulation of synoviocyte proliferation / neutrophil homeostasis ...regulation of B cell cytokine production / regulation of B cell apoptotic process / monocyte proliferation / positive regulation of interleukin-17A production / proteoglycan catabolic process / eosinophil homeostasis / positive regulation of type III hypersensitivity / negative regulation of B cell activation / positive regulation of synoviocyte proliferation / neutrophil homeostasis / histamine secretion by mast cell / negative regulation of leukocyte proliferation / positive regulation of type I hypersensitivity / positive regulation of cGAS/STING signaling pathway / cellular response to molecule of fungal origin / MyD88 deficiency (TLR2/4) / IRAK4 deficiency (TLR2/4) / negative regulation of interleukin-10 production / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / positive regulation of B cell differentiation / MyD88-dependent toll-like receptor signaling pathway / phospholipase activator activity / positive regulation of immunoglobulin production / mesoderm development / Fc-epsilon receptor signaling pathway / phosphatidylinositol-3,4,5-trisphosphate binding / B cell activation / positive regulation of NLRP3 inflammasome complex assembly / positive regulation of B cell proliferation / RHO GTPases Activate WASPs and WAVEs / phospholipase binding / peptidyl-tyrosine phosphorylation / FCERI mediated Ca+2 mobilization / B cell receptor signaling pathway / positive regulation of phagocytosis / apoptotic signaling pathway / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / calcium-mediated signaling / non-specific protein-tyrosine kinase / FCGR3A-mediated phagocytosis / cellular response to reactive oxygen species / non-membrane spanning protein tyrosine kinase activity / Regulation of actin dynamics for phagocytic cup formation / positive regulation of interleukin-6 production / T cell receptor signaling pathway / positive regulation of tumor necrosis factor production / G beta:gamma signalling through BTK / DAP12 signaling / G alpha (12/13) signalling events / response to lipopolysaccharide / ER-Phagosome pathway / protein tyrosine kinase activity / cytoplasmic vesicle / Potential therapeutics for SARS / G alpha (q) signalling events / adaptive immune response / positive regulation of canonical NF-kappaB signal transduction / intracellular signal transduction / membrane raft / innate immune response / perinuclear region of cytoplasm / DNA-templated transcription / zinc ion binding / ATP binding / identical protein 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 ...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 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-9AJ / Tyrosine-protein kinase BTK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.59 Å
AuthorsSteinbacher, S. / Eigenbrot, C.
CitationJournal: J. Med. Chem. / Year: 2018
Title: Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton's Tyrosine Kinase Inhibitor in Early Clinical Development.
Authors: Crawford, J.J. / Johnson, A.R. / Misner, D.L. / Belmont, L.D. / Castanedo, G. / Choy, R. / Coraggio, M. / Dong, L. / Eigenbrot, C. / Erickson, R. / Ghilardi, N. / Hau, J. / Katewa, A. / ...Authors: Crawford, J.J. / Johnson, A.R. / Misner, D.L. / Belmont, L.D. / Castanedo, G. / Choy, R. / Coraggio, M. / Dong, L. / Eigenbrot, C. / Erickson, R. / Ghilardi, N. / Hau, J. / Katewa, A. / Kohli, P.B. / Lee, W. / Lubach, J.W. / McKenzie, B.S. / Ortwine, D.F. / Schutt, L. / Tay, S. / Wei, B. / Reif, K. / Liu, L. / Wong, H. / Young, W.B.
History
DepositionApr 7, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 28, 2018Provider: repository / Type: Initial release
Revision 1.1Apr 4, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name
Revision 1.2Mar 13, 2024Group: Advisory / Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_unobs_or_zero_occ_atoms
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)32,95212
Polymers31,5981
Non-polymers1,35311
Water5,044280
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)72.867, 103.908, 38.464
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21212

-
Components

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


Mass: 31598.287 Da / Num. of mol.: 1 / Fragment: UNP residues 423-693
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BTK, AGMX1, ATK, BPK / Production host: Spodoptera (butterflies/moths)
References: UniProt: Q06187, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-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


Mass: 664.796 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C37H44N8O4
#3: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 280 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.3 Å3/Da / Density % sol: 46.62 %
Crystal growTemperature: 300 K / Method: vapor diffusion / pH: 6.5 / Details: PEG 5000 MME ammonium sulfate MES pH 6.5

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1.00004 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 24, 2010
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.00004 Å / Relative weight: 1
ReflectionResolution: 1.59→60 Å / Num. obs: 40127 / % possible obs: 100 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 7.8 % / Biso Wilson estimate: 14.6 Å2 / Rsym value: 0.069 / Net I/σ(I): 21.2

-
Processing

Software
NameVersionClassification
REFMAC5.8.0155refinement
XDSdata reduction
XSCALEdata scaling
REFMACphasing
RefinementResolution: 1.59→59.66 Å / Cor.coef. Fo:Fc: 0.956 / Cor.coef. Fo:Fc free: 0.943 / SU B: 4.174 / SU ML: 0.069 / Cross valid method: THROUGHOUT / ESU R: 0.099 / ESU R Free: 0.096 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.21576 3631 9 %RANDOM
Rwork0.18592 ---
obs0.18867 36493 99.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å
Displacement parametersBiso mean: 13.999 Å2
Baniso -1Baniso -2Baniso -3
1-0.15 Å20 Å20 Å2
2---0.04 Å20 Å2
3----0.11 Å2
Refinement stepCycle: 1 / Resolution: 1.59→59.66 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2214 0 91 280 2585
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0192477
X-RAY DIFFRACTIONr_bond_other_d00.022301
X-RAY DIFFRACTIONr_angle_refined_deg1.9061.9923351
X-RAY DIFFRACTIONr_angle_other_deg3.67735316
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3345296
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.36924.035114
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.86815433
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.9591513
X-RAY DIFFRACTIONr_chiral_restr0.1050.2343
X-RAY DIFFRACTIONr_gen_planes_refined0.0120.022779
X-RAY DIFFRACTIONr_gen_planes_other0.0170.02571
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.1141.3151148
X-RAY DIFFRACTIONr_mcbond_other2.1111.311147
X-RAY DIFFRACTIONr_mcangle_it2.6232.9611456
X-RAY DIFFRACTIONr_mcangle_other2.6232.9681457
X-RAY DIFFRACTIONr_scbond_it4.2121.8931329
X-RAY DIFFRACTIONr_scbond_other4.221.8441321
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other5.0663.8211882
X-RAY DIFFRACTIONr_long_range_B_refined6.55511.5753001
X-RAY DIFFRACTIONr_long_range_B_other6.43810.5392913
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.59→1.676 Å / Total num. of bins used: 10
RfactorNum. reflection% reflection
Rfree0.29 511 -
Rwork0.246 5272 -
obs--99.98 %
Refinement TLS params.Method: refined / Origin x: 16.5036 Å / Origin y: 15.5282 Å / Origin z: 5.8752 Å
111213212223313233
T0.007 Å20.0015 Å20.0009 Å2-0.0202 Å20.0007 Å2--0.006 Å2
L0.2172 °2-0.0666 °2-0.0057 °2-0.63 °2-0.0665 °2--0.3418 °2
S-0.0034 Å °-0.0318 Å °-0.0277 Å °0.0268 Å °0.0109 Å °0.0402 Å °0.0412 Å °-0.0003 Å °-0.0075 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A389 - 659
2X-RAY DIFFRACTION1A701

+
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