[English] 日本語
Yorodumi
- PDB-7n4r: Bruton's tyrosine kinase in complex with compound 21 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7n4r
TitleBruton's tyrosine kinase in complex with compound 21
ComponentsTyrosine-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 / 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 / B cell affinity maturation / cellular response to interleukin-7 / positive regulation of synoviocyte proliferation ...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 / B cell affinity maturation / cellular response to interleukin-7 / positive regulation of synoviocyte proliferation / neutrophil homeostasis / histamine secretion by mast cell / positive regulation of cGAS/STING signaling pathway / positive regulation of type I hypersensitivity / cellular response to molecule of fungal origin / MyD88 deficiency (TLR2/4) / IRAK4 deficiency (TLR2/4) / negative regulation of B cell proliferation / negative regulation of interleukin-10 production / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / MyD88-dependent toll-like receptor signaling pathway / positive regulation of B cell differentiation / : / phospholipase activator activity / positive regulation of immunoglobulin production / Fc-epsilon receptor signaling pathway / mesoderm development / positive regulation of NLRP3 inflammasome complex assembly / phosphatidylinositol-3,4,5-trisphosphate binding / B cell activation / RHO GTPases Activate WASPs and WAVEs / cell maturation / positive regulation of B cell proliferation / phospholipase binding / peptidyl-tyrosine phosphorylation / FCERI mediated Ca+2 mobilization / positive regulation of phagocytosis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / apoptotic signaling pathway / B cell receptor signaling pathway / 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 / positive regulation of tumor necrosis factor production / G beta:gamma signalling through BTK / DAP12 signaling / T cell receptor signaling pathway / 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 / 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-0BG / Tyrosine-protein kinase BTK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.62 Å
AuthorsMetrick, C.M. / Marcotte, D.J.
CitationJournal: Bioorg.Med.Chem. / Year: 2021
Title: Utilizing structure based drug design and metabolic soft spot identification to optimize the in vitro potency and in vivo pharmacokinetic properties leading to the discovery of novel ...Title: Utilizing structure based drug design and metabolic soft spot identification to optimize the in vitro potency and in vivo pharmacokinetic properties leading to the discovery of novel reversible Bruton's tyrosine kinase inhibitors.
Authors: Hopkins, B.T. / Bame, E. / Bell, N. / Bohnert, T. / Bowden-Verhoek, J.K. / Bui, M. / Cancilla, M.T. / Conlon, P. / Cullen, P. / Erlanson, D.A. / Fan, J. / Fuchs-Knotts, T. / Hansen, S. / ...Authors: Hopkins, B.T. / Bame, E. / Bell, N. / Bohnert, T. / Bowden-Verhoek, J.K. / Bui, M. / Cancilla, M.T. / Conlon, P. / Cullen, P. / Erlanson, D.A. / Fan, J. / Fuchs-Knotts, T. / Hansen, S. / Heumann, S. / Jenkins, T.J. / Gua, C. / Liu, Y. / Liu, Y. / Lulla, M. / Marcotte, D. / Marx, I. / McDowell, B. / Mertsching, E. / Negrou, E. / Romanowski, M.J. / Scott, D. / Silvian, L. / Yang, W. / Zhong, M.
History
DepositionJun 4, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 18, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 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: Tyrosine-protein kinase BTK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,8313
Polymers31,4281
Non-polymers4032
Water3,387188
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)71.800, 104.691, 38.053
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 Tyrosine-protein kinase BTK / Agammaglobulinemia tyrosine kinase / ATK / B-cell progenitor kinase / BPK / Bruton tyrosine kinase


Mass: 31428.078 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN
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-0BG / N-{2-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]ethyl}-N~2~-phenylglycinamide


Mass: 324.380 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H20N6O / 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.: 188 / 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: 45.94 %
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: 1 Å
DetectorType: RAYONIX MX-225 / Detector: CCD / Date: Mar 27, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.62→21.76 Å / Num. obs: 36187 / % possible obs: 96.6 % / Redundancy: 4.5 % / Biso Wilson estimate: 16.57 Å2 / Rmerge(I) obs: 0.136 / Net I/σ(I): 8.9
Reflection shellResolution: 1.62→1.71 Å / Rmerge(I) obs: 0.461 / Num. unique obs: 44630

-
Processing

Software
NameVersionClassification
PHENIX1.19.1_4122+SVNphasing
PHENIX1.19.1_4122+SVNrefinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5p9j

5p9j


Resolution: 1.62→21.56 Å / SU ML: 0.1806 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 22.0965
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2221 1784 4.99 %
Rwork0.1921 33990 -
obs0.1936 35774 96.69 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 19.92 Å2
Refinement stepCycle: LAST / Resolution: 1.62→21.56 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2041 0 28 188 2257
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0162178
X-RAY DIFFRACTIONf_angle_d1.4732950
X-RAY DIFFRACTIONf_chiral_restr0.0889314
X-RAY DIFFRACTIONf_plane_restr0.0145374
X-RAY DIFFRACTIONf_dihedral_angle_d14.4137811
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.62-1.670.29631150.23362263X-RAY DIFFRACTION84.75
1.67-1.720.22941130.21472541X-RAY DIFFRACTION94.65
1.72-1.770.27231370.20212530X-RAY DIFFRACTION95.35
1.77-1.840.2141510.18852585X-RAY DIFFRACTION97.89
1.84-1.910.27641290.23942582X-RAY DIFFRACTION96.65
1.91-20.29781300.23712539X-RAY DIFFRACTION94.51
2-2.10.271260.21652595X-RAY DIFFRACTION96.32
2.1-2.230.20581410.17592673X-RAY DIFFRACTION99.58
2.23-2.410.21491490.18192646X-RAY DIFFRACTION98.69
2.41-2.650.18581410.18792712X-RAY DIFFRACTION99.86
2.65-3.030.22711520.1992702X-RAY DIFFRACTION99.62
3.03-3.810.19551420.18292750X-RAY DIFFRACTION99.25
3.81-21.560.2111580.16882872X-RAY DIFFRACTION99.38

+
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