[English] 日本語
Yorodumi
- PDB-6toh: Crystal structure of human BCL6 BTB domain in complex with compound 6 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6toh
TitleCrystal structure of human BCL6 BTB domain in complex with compound 6
Components
  • ALA-TRP-VAL-ILE-PRO-ALA
  • B-cell lymphoma 6 protein
KeywordsTRANSCRIPTION / Cancer / Lymphoma / Inhibitor / Degrader
Function / homology
Function and homology information


regulation of memory T cell differentiation / negative regulation of mitotic cell cycle DNA replication / intronic transcription regulatory region sequence-specific DNA binding / negative regulation of isotype switching to IgE isotypes / negative regulation of plasma cell differentiation / negative regulation of T-helper 2 cell differentiation / isotype switching to IgE isotypes / negative regulation of mononuclear cell proliferation / negative regulation of mast cell cytokine production / regulation of germinal center formation ...regulation of memory T cell differentiation / negative regulation of mitotic cell cycle DNA replication / intronic transcription regulatory region sequence-specific DNA binding / negative regulation of isotype switching to IgE isotypes / negative regulation of plasma cell differentiation / negative regulation of T-helper 2 cell differentiation / isotype switching to IgE isotypes / negative regulation of mononuclear cell proliferation / negative regulation of mast cell cytokine production / regulation of germinal center formation / plasma cell differentiation / paraspeckles / germinal center formation / pyramidal neuron differentiation / regulation of immune system process / type 2 immune response / positive regulation of regulatory T cell differentiation / T-helper 2 cell differentiation / negative regulation of B cell apoptotic process / positive regulation of cell motility / negative regulation of Rho protein signal transduction / FOXO-mediated transcription of cell death genes / negative regulation of cell-matrix adhesion / regulation of T cell proliferation / negative regulation of Notch signaling pathway / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / B cell proliferation / regulation of cell differentiation / negative regulation of cellular senescence / Rho protein signal transduction / regulation of immune response / erythrocyte development / heterochromatin formation / positive regulation of B cell proliferation / regulation of cytokine production / positive regulation of neuron differentiation / cell-matrix adhesion / transcription corepressor binding / cell motility / cell morphogenesis / protein localization / negative regulation of cell growth / chromatin DNA binding / DNA-binding transcription repressor activity, RNA polymerase II-specific / sequence-specific double-stranded DNA binding / regulation of cell population proliferation / regulation of inflammatory response / actin cytoskeleton organization / spermatogenesis / Interleukin-4 and Interleukin-13 signaling / DNA-binding transcription factor binding / sequence-specific DNA binding / transcription by RNA polymerase II / inflammatory response / positive regulation of apoptotic process / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / negative regulation of DNA-templated transcription / DNA damage response / chromatin binding / nucleolus / Golgi apparatus / negative regulation of transcription by RNA polymerase II / nucleoplasm / identical protein binding / nucleus / metal ion binding
Similarity search - Function
Potassium Channel Kv1.1; Chain A / Potassium Channel Kv1.1; Chain A / BTB/POZ domain / BTB domain profile. / Zinc finger, C2H2 type / Broad-Complex, Tramtrack and Bric a brac / BTB/POZ domain / zinc finger / Zinc finger C2H2 type domain profile. / Zinc finger C2H2 superfamily ...Potassium Channel Kv1.1; Chain A / Potassium Channel Kv1.1; Chain A / BTB/POZ domain / BTB domain profile. / Zinc finger, C2H2 type / Broad-Complex, Tramtrack and Bric a brac / BTB/POZ domain / zinc finger / Zinc finger C2H2 type domain profile. / Zinc finger C2H2 superfamily / SKP1/BTB/POZ domain superfamily / Zinc finger C2H2 type domain signature. / Zinc finger C2H2-type / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-NQK / B-cell lymphoma 6 protein
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.58 Å
AuthorsCollie, G.W. / Shetty, K. / Rodrigues, M.J. / Le Bihan, Y.-V. / van Montfort, R.L.M.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Cancer Research UKC309/A11566 United Kingdom
CitationJournal: J.Med.Chem. / Year: 2020
Title: AchievingIn VivoTarget Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders.
Authors: Bellenie, B.R. / Cheung, K.J. / Varela, A. / Pierrat, O.A. / Collie, G.W. / Box, G.M. / Bright, M.D. / Gowan, S. / Hayes, A. / Rodrigues, M.J. / Shetty, K.N. / Carter, M. / Davis, O.A. / ...Authors: Bellenie, B.R. / Cheung, K.J. / Varela, A. / Pierrat, O.A. / Collie, G.W. / Box, G.M. / Bright, M.D. / Gowan, S. / Hayes, A. / Rodrigues, M.J. / Shetty, K.N. / Carter, M. / Davis, O.A. / Henley, A.T. / Innocenti, P. / Johnson, L.D. / Liu, M. / de Klerk, S. / Le Bihan, Y.V. / Lloyd, M.G. / McAndrew, P.C. / Shehu, E. / Talbot, R. / Woodward, H.L. / Burke, R. / Kirkin, V. / van Montfort, R.L.M. / Raynaud, F.I. / Rossanese, O.W. / Hoelder, S.
History
DepositionDec 11, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 22, 2020Provider: repository / Type: Initial release
Revision 1.1May 6, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Jan 24, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: B-cell lymphoma 6 protein
B: ALA-TRP-VAL-ILE-PRO-ALA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)15,7557
Polymers15,1932
Non-polymers5625
Water3,081171
1
A: B-cell lymphoma 6 protein
B: ALA-TRP-VAL-ILE-PRO-ALA
hetero molecules

A: B-cell lymphoma 6 protein
B: ALA-TRP-VAL-ILE-PRO-ALA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,50914
Polymers30,3854
Non-polymers1,12410
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation12_545x,x-y-1,-z+1/61
Buried area6150 Å2
ΔGint-36 kcal/mol
Surface area13590 Å2
MethodPISA
Unit cell
Length a, b, c (Å)67.785, 67.785, 165.983
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number178
Space group name H-MP6122
Components on special symmetry positions
IDModelComponents
11A-356-

HOH

-
Components

#1: Protein B-cell lymphoma 6 protein / BCL-6 / B-cell lymphoma 5 protein / BCL-5 / Protein LAZ-3 / Zinc finger and BTB domain-containing ...BCL-6 / B-cell lymphoma 5 protein / BCL-5 / Protein LAZ-3 / Zinc finger and BTB domain-containing protein 27 / Zinc finger protein 51


Mass: 14536.915 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BCL6, BCL5, LAZ3, ZBTB27, ZNF51 / Plasmid: pET48b / Production host: Escherichia coli BL21 (bacteria) / Variant (production host): AI / References: UniProt: P41182
#2: Protein/peptide ALA-TRP-VAL-ILE-PRO-ALA


Mass: 655.784 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#3: Chemical ChemComp-NQK / 2-chloranyl-4-[(1,3-dimethyl-2-oxidanylidene-benzimidazol-5-yl)amino]pyridine-3-carbonitrile


Mass: 313.742 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H12ClN5O / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 171 / 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: 3.69 Å3/Da / Density % sol: 66.68 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 2 microlitre of the BCL6-BTB/WVIP complex at 4 mg/mL plus 1 microliter of a crystallisation solution consisting of 1 M K2HPO4, 0.7 M NaH2PO4, 75 mM sodium acetate buffer pH 4.5 and 2 % DMSO, ...Details: 2 microlitre of the BCL6-BTB/WVIP complex at 4 mg/mL plus 1 microliter of a crystallisation solution consisting of 1 M K2HPO4, 0.7 M NaH2PO4, 75 mM sodium acetate buffer pH 4.5 and 2 % DMSO, against 350 microliter of crystallisation solution.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: MASSIF-1 / Wavelength: 0.966 Å
DetectorType: DECTRIS PILATUS3 2M / Detector: PIXEL / Date: Aug 7, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.966 Å / Relative weight: 1
ReflectionResolution: 1.58→47.93 Å / Num. obs: 31907 / % possible obs: 100 % / Redundancy: 18.8 % / Biso Wilson estimate: 30.07 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.074 / Rpim(I) all: 0.018 / Rrim(I) all: 0.076 / Net I/σ(I): 21 / Num. measured all: 598830
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.58-1.6419.42.1685922930480.6770.4982.2251.7100
6.12-47.9315.50.044106466860.9990.0110.0465999.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
BUSTER2.10.3refinement
XDSdata reduction
Aimless0.5.26data scaling
PHASERphasing
PDB_EXTRACT3.24data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3BIM

3bim


Resolution: 1.58→47.93 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.952 / SU R Cruickshank DPI: 0.061 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.068 / SU Rfree Blow DPI: 0.069 / SU Rfree Cruickshank DPI: 0.063
RfactorNum. reflection% reflectionSelection details
Rfree0.197 1546 4.86 %RANDOM
Rwork0.173 ---
obs0.174 31818 100 %-
Displacement parametersBiso max: 109.69 Å2 / Biso mean: 36.29 Å2 / Biso min: 18.94 Å2
Baniso -1Baniso -2Baniso -3
1--1.4524 Å20 Å20 Å2
2---1.4524 Å20 Å2
3---2.9048 Å2
Refine analyzeLuzzati coordinate error obs: 0.2 Å
Refinement stepCycle: final / Resolution: 1.58→47.93 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1008 0 38 177 1223
Biso mean--41.34 52.37 -
Num. residues----130
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d421SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes223HARMONIC5
X-RAY DIFFRACTIONt_it1173HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion156SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies14HARMONIC1
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact1557SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d1173HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg1596HARMONIC20.98
X-RAY DIFFRACTIONt_omega_torsion3.47
X-RAY DIFFRACTIONt_other_torsion13.08
LS refinement shellResolution: 1.58→1.59 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.261 35 5.49 %
Rwork0.2279 602 -
all0.2298 637 -
obs--99.68 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
14.20090.70472.571.3641.36945.38550.0569-0.0219-0.20460.1412-0.02250.04340.282-0.3386-0.0344-0.0405-0.03010.0045-0.0458-0.0188-0.066629.1184-28.188413.3282
20.90730.14320.65242.35860.77660.83570.1251-0.12890.07640.20550.1831-0.4309-0.1360.2712-0.30820.0882-0.0267-0.03120.0866-0.05420.038541.225-14.869327.9302
32.33940.2621.5861.78590.14121.63750.0849-0.23950.01790.31720.0403-0.1135-0.17410.1743-0.1252-0.0067-0.0312-0.0201-0.0492-0.0326-0.105139.6187-15.975629.0988
41.52511.1119-0.35543.23491.49572.93660.05370.02940.171-0.08820.0644-0.0225-0.37780.0686-0.11810.0596-0.03260.0359-0.0611-0.0175-0.010434.9631-7.009822.2896
51.12491.09260.10023.68642.90743.62040.1601-0.1927-0.08410.5228-0.0903-0.06230.20220.0234-0.06980.0051-0.05370.0189-0.0469-0.0121-0.065429.6377-18.774928.5205
62.57491.6474-0.62771.1046-1.8672.07560.0969-0.24110.02570.3988-0.24110.24390.08480.19160.14420.1041-0.10240.06980.0259-0.0272-0.026422.1729-22.556532.477
72.97232.4313-1.16924.9011-0.76474.40420.3003-0.21230.33960.3908-0.32030.4121-0.147-0.43680.02-0.0472-0.04490.0775-0.0859-0.0699-0.067623.4858-10.4830.9071
87.4785-0.0683-3.13297.00721.03710.0901-0.00310.15830.23940.1099-0.15550.67390.2279-0.47890.1586-0.0198-0.07470.09160.0903-0.11410.103513.699-14.448131.0653
96.35772.44020.51560.69843.65060.02340.07950.0362-0.0482-0.12810.03440.16690.08190.0408-0.1139-0.066-0.0528-0.01410.08-0.0517-0.003419.1353-31.64982.4038
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{A|6 - 27}A6 - 27
2X-RAY DIFFRACTION2{A|28 - 40}A28 - 40
3X-RAY DIFFRACTION3{A|41 - 46}A41 - 46
4X-RAY DIFFRACTION4{A|47 - 79}A47 - 79
5X-RAY DIFFRACTION5{A|80 - 92}A80 - 92
6X-RAY DIFFRACTION6{A|93 - 101}A93 - 101
7X-RAY DIFFRACTION7{A|102 - 114}A102 - 114
8X-RAY DIFFRACTION8{A|115 - 129}A115 - 129
9X-RAY DIFFRACTION9{B|0 - 5}B0 - 5

+
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://pdbjlvh1.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