[English] 日本語
Yorodumi
- PDB-6uve: Crystal structure of BCL-XL bound to compound 7: (R)-3-(Benzylthi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6uve
TitleCrystal structure of BCL-XL bound to compound 7: (R)-3-(Benzylthio)-2-(3-(4-chloro-[1,1':2',1'':3'',1'''-quaterphenyl]-4'''-carbonyl)-3-(4-methylbenzyl)ureido)propanoic acid
ComponentsBcl-2-like protein 1
KeywordsApoptosis/INHIBITOR / Apoptosis / BCL-2 family / BCL-XL / inhibitor / Apoptosis-INHIBITOR complex
Function / homology
Function and homology information


apoptotic process in bone marrow cell / SARS-CoV-1-mediated effects on programmed cell death / The NLRP1 inflammasome / dendritic cell apoptotic process / dendritic cell proliferation / positive regulation of mononuclear cell proliferation / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of execution phase of apoptosis / negative regulation of dendritic cell apoptotic process ...apoptotic process in bone marrow cell / SARS-CoV-1-mediated effects on programmed cell death / The NLRP1 inflammasome / dendritic cell apoptotic process / dendritic cell proliferation / positive regulation of mononuclear cell proliferation / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of execution phase of apoptosis / negative regulation of dendritic cell apoptotic process / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / fertilization / regulation of mitochondrial membrane permeability / regulation of growth / negative regulation of protein localization to plasma membrane / Bcl-2 family protein complex / BH domain binding / NFE2L2 regulating tumorigenic genes / response to cycloheximide / STAT5 activation downstream of FLT3 ITD mutants / cellular response to alkaloid / hepatocyte apoptotic process / negative regulation of release of cytochrome c from mitochondria / negative regulation of reproductive process / negative regulation of developmental process / BH3 domain binding / germ cell development / apoptotic mitochondrial changes / negative regulation of anoikis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / ectopic germ cell programmed cell death / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / negative regulation of intrinsic apoptotic signaling pathway / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / ovarian follicle development / extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of autophagy / release of cytochrome c from mitochondria / regulation of cytokinesis / regulation of mitochondrial membrane potential / epithelial cell proliferation / response to cytokine / cellular response to amino acid stimulus / cellular response to gamma radiation / synaptic vesicle membrane / RAS processing / endocytosis / male gonad development / intrinsic apoptotic signaling pathway in response to DNA damage / spermatogenesis / nuclear membrane / Interleukin-4 and Interleukin-13 signaling / neuron apoptotic process / defense response to virus / in utero embryonic development / negative regulation of neuron apoptotic process / mitochondrial outer membrane / mitochondrial inner membrane / mitochondrial matrix / centrosome / negative regulation of apoptotic process / protein kinase binding / endoplasmic reticulum / mitochondrion / identical protein binding / cytosol / cytoplasm
Similarity search - Function
Apoptosis regulator, Bcl-X / Apoptosis regulator, Bcl-2/ BclX / Apoptosis regulator, Bcl-2, BH4 motif, conserved site / Apoptosis regulator, Bcl-2 family BH4 motif signature. / Apoptosis regulator, Bcl-2 protein, BH4 / Bcl-2 homology region 4 / Apoptosis regulator, Bcl-2 family BH4 motif profile. / BH4 Bcl-2 homology region 4 / Apoptosis regulator, Bcl-2, BH3 motif, conserved site / Apoptosis regulator, Bcl-2 family BH3 motif signature. ...Apoptosis regulator, Bcl-X / Apoptosis regulator, Bcl-2/ BclX / Apoptosis regulator, Bcl-2, BH4 motif, conserved site / Apoptosis regulator, Bcl-2 family BH4 motif signature. / Apoptosis regulator, Bcl-2 protein, BH4 / Bcl-2 homology region 4 / Apoptosis regulator, Bcl-2 family BH4 motif profile. / BH4 Bcl-2 homology region 4 / Apoptosis regulator, Bcl-2, BH3 motif, conserved site / Apoptosis regulator, Bcl-2 family BH3 motif signature. / Apoptosis regulator, Bcl-2, BH1 motif, conserved site / Apoptosis regulator, Bcl-2 family BH1 motif signature. / Apoptosis regulator, Bcl-2, BH2 motif, conserved site / Apoptosis regulator, Bcl-2 family BH2 motif signature. / BCL (B-Cell lymphoma); contains BH1, BH2 regions / Bcl-2 family / Bcl-2, Bcl-2 homology region 1-3 / Bcl2-like / Apoptosis regulator proteins, Bcl-2 family / BCL2-like apoptosis inhibitors family profile. / Bcl-2-like superfamily
Similarity search - Domain/homology
Chem-QHV / Bcl-2-like protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.87 Å
AuthorsRoy, M.J. / Lessene, G. / Czabotar, P.E.
Funding support Australia, 1items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia) Australia
CitationJournal: J.Med.Chem. / Year: 2021
Title: Structure-Guided Development of Potent Benzoylurea Inhibitors of BCL-X L and BCL-2.
Authors: Roy, M.J. / Vom, A. / Okamoto, T. / Smith, B.J. / Birkinshaw, R.W. / Yang, H. / Abdo, H. / White, C.A. / Segal, D. / Huang, D.C.S. / Baell, J.B. / Colman, P.M. / Czabotar, P.E. / Lessene, G.
History
DepositionNov 2, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 5, 2021Provider: repository / Type: Initial release
Revision 1.1May 12, 2021Group: Database references / Category: citation / citation_author / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2May 26, 2021Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Oct 11, 2023Group: 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: Bcl-2-like protein 1
B: Bcl-2-like protein 1
C: Bcl-2-like protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,9927
Polymers53,7543
Non-polymers2,2384
Water32418
1
A: Bcl-2-like protein 1
B: Bcl-2-like protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,3495
Polymers35,8362
Non-polymers1,5133
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4140 Å2
ΔGint-28 kcal/mol
Surface area13630 Å2
MethodPISA
2
C: Bcl-2-like protein 1
hetero molecules

C: Bcl-2-like protein 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,2874
Polymers35,8362
Non-polymers1,4512
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation8_664-y+1,-x+1,-z-1/21
Buried area4360 Å2
ΔGint-29 kcal/mol
Surface area14320 Å2
MethodPISA
Unit cell
Length a, b, c (Å)148.571, 148.571, 57.448
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number96
Space group name H-MP43212

-
Components

#1: Protein Bcl-2-like protein 1 / Bcl2-L-1 / Apoptosis regulator Bcl-X


Mass: 17917.959 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BCL2L1, BCL2L, BCLX / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q07817
#2: Chemical ChemComp-QHV / (R)-3-(Benzylthio)-2-(3-(4-chloro-[1,1':2',1'':3'',1'''-quaterphenyl]-4'''-carbonyl)-3-(4-methylbenzyl)ureido)propanoic acid


Mass: 725.294 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C44H37ClN2O4S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 18 / 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: 2.95 Å3/Da / Density % sol: 58.29 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 0.9 M trisodium citrate, 0.1 M MES pH 6.0, 5% (v/v) PEG400

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9537 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 29, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 2.87→25.48 Å / Num. obs: 14966 / % possible obs: 98.6 % / Redundancy: 14.007 % / Biso Wilson estimate: 80.49 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.294 / Rrim(I) all: 0.305 / Χ2: 0.984 / Net I/σ(I): 12.83 / Num. measured all: 209623
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
2.87-3.0513.2721.7461.9428893239021770.6271.81391.1
3.05-3.2614.5771.2483.3432945226022600.8221.293100
3.26-3.5214.4720.8275.8830435210321030.9390.857100
3.52-3.8514.3510.4510.5228199196519650.9810.466100
3.85-4.3114.2380.2715.6825258177417740.9930.28100
4.31-4.9714.1950.16321.7922471158315830.9960.169100
4.97-6.0813.9280.15721.3918914135813580.9960.163100
6.08-8.5713.3320.09926.1514492108710870.9990.103100
8.57-25.4812.1640.04941.6580166606590.9980.05199.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XDSdata reduction
XSCALEdata scaling
PHASERphasing
BUSTERrefinement
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2YXJ

2yxj


Resolution: 2.87→25.48 Å / Cor.coef. Fo:Fc: 0.911 / Cor.coef. Fo:Fc free: 0.875 / SU R Cruickshank DPI: 0.998 / Cross valid method: FREE R-VALUE / σ(F): 0 / SU R Blow DPI: 1.033 / SU Rfree Blow DPI: 0.345 / SU Rfree Cruickshank DPI: 0.349
RfactorNum. reflection% reflectionSelection details
Rfree0.254 747 5 %RANDOM
Rwork0.213 ---
obs0.215 14934 98.5 %-
Displacement parametersBiso max: 143.85 Å2 / Biso mean: 62.89 Å2 / Biso min: 27.82 Å2
Baniso -1Baniso -2Baniso -3
1--3.0409 Å20 Å20 Å2
2---3.0409 Å20 Å2
3---6.0818 Å2
Refine analyzeLuzzati coordinate error obs: 0.4 Å
Refinement stepCycle: final / Resolution: 2.87→25.48 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3234 0 160 18 3412
Biso mean--67.28 43.67 -
Num. residues----415
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1136SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes728HARMONIC5
X-RAY DIFFRACTIONt_it3486HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion408SEMIHARMONIC5
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_contact4108SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d3486HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg4729HARMONIC21.05
X-RAY DIFFRACTIONt_omega_torsion2.58
X-RAY DIFFRACTIONt_other_torsion20.86
LS refinement shellResolution: 2.87→2.92 Å / Rfactor Rfree error: 0 / Total num. of bins used: 37
RfactorNum. reflection% reflection
Rfree0.4247 20 4.95 %
Rwork0.3149 384 -
all0.3194 404 -
obs--64.33 %
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)
12.63260.2254-1.39572.9196-0.39573.9084-0.04330.0934-0.4558-0.1474-0.0643-0.37790.38680.52080.1076-0.08450.00990.0352-0.1389-0.0365-0.122623.932990.2043-6.3296
25.045-0.0474-1.44081.9858-0.57093.4137-0.07990.1292-0.1278-0.12350.21740.28970.044-0.5598-0.1374-0.1047-0.0611-0.0071-0.12740.0676-0.16534.615798.97945.7825
32.46030.96080.36232.2097-0.1443.0646-0.12720.29620.0637-0.21380.03770.13290.1321-0.24320.0894-0.0667-0.19630.0363-0.0127-0.0074-0.192420.8047112.841-20.1223
41.680.82320.24511.3457-1.92042.8615-0.0385-0.2035-0.1742-0.1870.06-0.22780.20610.1444-0.0215-0.142-0.1321-0.0115-0.0872-0.01550.012117.679993.6961-3.3341
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|0 - A|196 }A0 - 196
2X-RAY DIFFRACTION2{ B|4 - B|201 }B4 - 201
3X-RAY DIFFRACTION3{ C|3 - C|206 }C3 - 206
4X-RAY DIFFRACTION4{ A|301 - A|301 C|301 - C|301 B|301 - B|301 }A301
5X-RAY DIFFRACTION4{ A|301 - A|301 C|301 - C|301 B|301 - B|301 }C301
6X-RAY DIFFRACTION4{ A|301 - A|301 C|301 - C|301 B|301 - B|301 }B301

+
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://pdbjlc1.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