[English] 日本語
Yorodumi
- PDB-5t18: Crystal structure of Bruton agammabulinemia tyrosine kinase compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5t18
TitleCrystal structure of Bruton agammabulinemia tyrosine kinase complexed with BMS-986142 aka (2s)-6-fluoro-5-[3-(8-fluoro-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-3-yl)-2-methylphenyl]-2-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1h-carbazole-8-carboxamide
ComponentsTyrosine-protein kinase BTK
KeywordsTRANSFERASE / KINASE / BTK / ATK / XLA / PSCTK1 / AGMX1 / AT / IMD1 / MGC126261 / MGC126262 BPK / ----
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 / histamine secretion by mast cell / positive regulation of synoviocyte proliferation ...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 / histamine secretion by mast cell / positive regulation of synoviocyte proliferation / neutrophil homeostasis / cellular response to molecule of fungal origin / positive regulation of type I hypersensitivity / cellular response to interleukin-7 / MyD88 deficiency (TLR2/4) / MyD88-dependent toll-like receptor signaling pathway / IRAK4 deficiency (TLR2/4) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / positive regulation of B cell differentiation / positive regulation of NLRP3 inflammasome complex assembly / phospholipase activator activity / negative regulation of interleukin-10 production / B cell activation / negative regulation of B cell proliferation / Fc-epsilon receptor signaling pathway / phosphatidylinositol-3,4,5-trisphosphate binding / phospholipase binding / mesoderm development / positive regulation of immunoglobulin production / 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 / calcium-mediated signaling / apoptotic signaling pathway / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / G beta:gamma signalling through BTK / Regulation of actin dynamics for phagocytic cup formation / cellular response to reactive oxygen species / positive regulation of interleukin-6 production / peptidyl-tyrosine phosphorylation / G alpha (12/13) signalling events / positive regulation of tumor necrosis factor production / DAP12 signaling / positive regulation of NF-kappaB transcription factor activity / ER-Phagosome pathway / T cell receptor signaling pathway / cytoplasmic vesicle / G alpha (q) signalling events / protein tyrosine kinase activity / Potential therapeutics for SARS / response to lipopolysaccharide / adaptive immune response / intracellular signal transduction / membrane raft / protein phosphorylation / innate immune response / 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 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; 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-73T / Tyrosine-protein kinase BTK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.5 Å
AuthorsMuckelbauer, J.K.
CitationJournal: J. Med. Chem. / Year: 2016
Title: Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (BMS- ...Title: Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide (BMS-986142): A Reversible Inhibitor of Bruton's Tyrosine Kinase (BTK) Conformationally Constrained by Two Locked Atropisomers.
Authors: Watterson, S.H. / De Lucca, G.V. / Shi, Q. / Langevine, C.M. / Liu, Q. / Batt, D.G. / Beaudoin Bertrand, M. / Gong, H. / Dai, J. / Yip, S. / Li, P. / Sun, D. / Wu, D.R. / Wang, C. / Zhang, Y. ...Authors: Watterson, S.H. / De Lucca, G.V. / Shi, Q. / Langevine, C.M. / Liu, Q. / Batt, D.G. / Beaudoin Bertrand, M. / Gong, H. / Dai, J. / Yip, S. / Li, P. / Sun, D. / Wu, D.R. / Wang, C. / Zhang, Y. / Traeger, S.C. / Pattoli, M.A. / Skala, S. / Cheng, L. / Obermeier, M.T. / Vickery, R. / Discenza, L.N. / D'Arienzo, C.J. / Zhang, Y. / Heimrich, E. / Gillooly, K.M. / Taylor, T.L. / Pulicicchio, C. / McIntyre, K.W. / Galella, M.A. / Tebben, A.J. / Muckelbauer, J.K. / Chang, C. / Rampulla, R. / Mathur, A. / Salter-Cid, L. / Barrish, J.C. / Carter, P.H. / Fura, A. / Burke, J.R. / Tino, J.A.
History
DepositionAug 18, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 8, 2017Provider: repository / Type: Initial release
Revision 1.1Mar 6, 2024Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_radiation_wavelength
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)31,7772
Polymers31,2041
Non-polymers5731
Water2,648147
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area11780 Å2
MethodPISA
Unit cell
Length a, b, c (Å)46.604, 69.759, 88.955
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 31203.910 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: baculovirus / Strain (production host): sf9
References: UniProt: Q06187, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-73T / 6-Fluoro-5-(R)-(3-(S)-(8-fluoro-1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)-2-methylphenyl)-2-(S)-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide / (2S)-6-fluoro-5-[3-(8-fluoro-1-methyl-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-2-methylphenyl]-2-(2-hydroxypropan-2-yl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxamide


Mass: 572.602 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C32H30F2N4O4
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 147 / 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: 2.32 Å3/Da / Density % sol: 46.91 % / Mosaicity: 0.461 °
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 7 / Details: 25% PEG8K + 3% MEPEG5K + 0.2M TRIS-HCL, PH 7.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 0.98 Å
DetectorType: RAYONIX MX-300 / Detector: CCD / Date: May 24, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98 Å / Relative weight: 1
ReflectionResolution: 1.5→50 Å / Num. obs: 46852 / % possible obs: 99.6 % / Observed criterion σ(I): 0 / Redundancy: 5.9 % / Biso Wilson estimate: 23.37 Å2 / Rmerge(I) obs: 0.071 / Χ2: 1.047 / Net I/av σ(I): 21.334 / Net I/σ(I): 21.3 / Num. measured all: 276987
Reflection shellResolution: 1.5→1.55 Å / Redundancy: 6 % / Rmerge(I) obs: 0.627 / Mean I/σ(I) obs: 3.7 / % possible all: 100

-
Processing

Software
NameVersionClassification
BUSTER-TNT2.11.7refinement
SCALEPACKdata scaling
PDB_EXTRACT3.2data extraction
RefinementResolution: 1.5→30 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.949 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.081 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.074 / SU Rfree Blow DPI: 0.073 / SU Rfree Cruickshank DPI: 0.072
RfactorNum. reflection% reflectionSelection details
Rfree0.223 2364 5.05 %RANDOM
Rwork0.203 ---
obs0.204 46785 99.1 %-
Displacement parametersBiso max: 75.89 Å2 / Biso mean: 24.9 Å2 / Biso min: 11.61 Å2
Baniso -1Baniso -2Baniso -3
1--1.4472 Å20 Å20 Å2
2--0.8509 Å20 Å2
3---0.5963 Å2
Refine analyzeLuzzati coordinate error obs: 0.2 Å
Refinement stepCycle: final / Resolution: 1.5→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1974 0 72 147 2193
Biso mean--18.21 33.7 -
Num. residues----261
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d832SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes34HARMONIC2
X-RAY DIFFRACTIONt_gen_planes644HARMONIC5
X-RAY DIFFRACTIONt_it3932HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion269SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact4375SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d3932HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg7064HARMONIC21.06
X-RAY DIFFRACTIONt_omega_torsion4.07
X-RAY DIFFRACTIONt_other_torsion13.45
LS refinement shellResolution: 1.5→1.54 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.262 176 5.52 %
Rwork0.211 3013 -
all-3189 -
obs--93.37 %

+
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