[English] 日本語
Yorodumi
- PDB-7lty: Bruton's tyrosine kinase in complex with compound 23 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7lty
TitleBruton's tyrosine kinase in complex with compound 23
ComponentsIsoform BTK-C of Tyrosine-protein kinase BTK
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / transferase / transferase inhibitor / kinase / kinase inhibitor / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


regulation of B cell cytokine production / proteoglycan catabolic process / monocyte proliferation / positive regulation of interleukin-17A production / regulation of B cell apoptotic process / eosinophil homeostasis / positive regulation of type III hypersensitivity / B cell affinity maturation / positive regulation of synoviocyte proliferation / histamine secretion by mast cell ...regulation of B cell cytokine production / proteoglycan catabolic process / monocyte proliferation / positive regulation of interleukin-17A production / regulation of B cell apoptotic process / 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 / MyD88 deficiency (TLR2/4) / cellular response to interleukin-7 / MyD88-dependent toll-like receptor signaling pathway / IRAK4 deficiency (TLR2/4) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / positive regulation of immunoglobulin production / positive regulation of B cell differentiation / positive regulation of NLRP3 inflammasome complex assembly / phospholipase activator activity / negative regulation of interleukin-10 production / negative regulation of B cell proliferation / mesoderm development / Fc-epsilon receptor signaling pathway / B cell activation / phosphatidylinositol-3,4,5-trisphosphate binding / phospholipase binding / RHO GTPases Activate WASPs and WAVEs / positive regulation of phagocytosis / positive regulation of B cell proliferation / cell maturation / FCERI mediated Ca+2 mobilization / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / apoptotic signaling pathway / non-specific protein-tyrosine kinase / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / non-membrane spanning protein tyrosine kinase activity / calcium-mediated signaling / Regulation of actin dynamics for phagocytic cup formation / peptidyl-tyrosine phosphorylation / G beta:gamma signalling through BTK / positive regulation of interleukin-6 production / cellular response to reactive oxygen species / positive regulation of tumor necrosis factor production / G alpha (12/13) signalling events / DAP12 signaling / positive regulation of NF-kappaB transcription factor activity / T cell receptor signaling pathway / ER-Phagosome pathway / cytoplasmic vesicle / protein tyrosine kinase activity / G alpha (q) signalling events / adaptive immune response / response to lipopolysaccharide / Potential therapeutics for SARS / intracellular signal transduction / protein phosphorylation / membrane raft / innate immune response / perinuclear region of cytoplasm / ATP binding / identical protein binding / nucleus / metal ion binding / 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. / Tyrosine-protein kinase, active site / PH-like domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / 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-YD7 / Tyrosine-protein kinase BTK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.69 Å
AuthorsMetrick, C.M. / Marcotte, D.J.
CitationJournal: J.Med.Chem. / Year: 2022
Title: Discovery and Preclinical Characterization of BIIB091, a Reversible, Selective BTK Inhibitor for the Treatment of Multiple Sclerosis.
Authors: Hopkins, B.T. / Bame, E. / Bajrami, B. / Black, C. / Bohnert, T. / Boiselle, C. / Burdette, D. / Burns, J.C. / Delva, L. / Donaldson, D. / Grater, R. / Gu, C. / Hoemberger, M. / Johnson, J. ...Authors: Hopkins, B.T. / Bame, E. / Bajrami, B. / Black, C. / Bohnert, T. / Boiselle, C. / Burdette, D. / Burns, J.C. / Delva, L. / Donaldson, D. / Grater, R. / Gu, C. / Hoemberger, M. / Johnson, J. / Kapadnis, S. / King, K. / Lulla, M. / Ma, B. / Marx, I. / Magee, T. / Meissner, R. / Metrick, C.M. / Mingueneau, M. / Murugan, P. / Otipoby, K.L. / Polack, E. / Poreci, U. / Prince, R. / Roach, A.M. / Rowbottom, C. / Santoro, J.C. / Schroeder, P. / Tang, H. / Tien, E. / Zhang, F. / Lyssikatos, J.
History
DepositionFeb 20, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 12, 2022Provider: repository / Type: Initial release
Revision 1.1Feb 9, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID
Revision 1.2Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform BTK-C of Tyrosine-protein kinase BTK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,7623
Polymers31,2081
Non-polymers5542
Water3,531196
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: surface plasmon resonance
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)71.478, 104.178, 38.165
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Space group name HallP22ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x+1/2,y+1/2,-z
#4: -x,-y,z

-
Components

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


Mass: 31207.855 Da / Num. of mol.: 1 / Fragment: Protein kinase domain, residues 427-693
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BTK, AGMX1, ATK, BPK / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q06187, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-YD7 / ~{N}-[(5~{R})-2-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-6,7,8,9-tetrahydro-5~{H}-benzo[7]annulen-5-yl]-3-propan-2-yloxy-azetidine-1-carboxamide


Mass: 475.586 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H33N7O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 196 / 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: 2.28 Å3/Da / Density % sol: 45.97 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.1M BisTRIS pH 6.5, 0.2M Ammonium Acetate, 0.1M Guanidine HCl, 20% PEG2200 MME

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.979 Å
DetectorType: RAYONIX MX-225 / Detector: CCD / Date: Nov 7, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 1.69→19.65 Å / Num. obs: 32678 / % possible obs: 98.9 % / Redundancy: 6.8 % / Biso Wilson estimate: 17.3 Å2 / Rmerge(I) obs: 0.117 / Net I/σ(I): 8.5
Reflection shellResolution: 1.69→1.75 Å / Rmerge(I) obs: 0.669 / Num. unique obs: 4380

-
Processing

Software
NameVersionClassification
PHENIX1.19_4080refinement
PHENIXphasing
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3GEN

3gen


Resolution: 1.69→19.65 Å / SU ML: 0.1912 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 20.2372
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.208 1606 4.92 %
Rwork0.1779 31023 -
obs0.1794 32629 98.88 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 22.18 Å2
Refinement stepCycle: LAST / Resolution: 1.69→19.65 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2076 0 39 196 2311
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01432217
X-RAY DIFFRACTIONf_angle_d1.37983000
X-RAY DIFFRACTIONf_chiral_restr0.0835315
X-RAY DIFFRACTIONf_plane_restr0.0123379
X-RAY DIFFRACTIONf_dihedral_angle_d15.5404845
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.69-1.740.32611230.28582515X-RAY DIFFRACTION88.97
1.74-1.80.28221560.25312758X-RAY DIFFRACTION99.22
1.8-1.870.24121300.2072803X-RAY DIFFRACTION100
1.87-1.960.22561450.19092798X-RAY DIFFRACTION100
1.96-2.060.22961500.18272828X-RAY DIFFRACTION100
2.06-2.190.23251360.17522840X-RAY DIFFRACTION100
2.19-2.360.1821260.16582863X-RAY DIFFRACTION99.97
2.36-2.60.20961410.17112862X-RAY DIFFRACTION100
2.6-2.970.21061590.18232857X-RAY DIFFRACTION100
2.97-3.740.19351660.16772888X-RAY DIFFRACTION100
3.74-19.650.18131740.15743011X-RAY DIFFRACTION99.41

+
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