[English] 日本語
Yorodumi
- PDB-4ieh: Crystal Structure of human Bcl-2 in complex with a small molecule... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ieh
TitleCrystal Structure of human Bcl-2 in complex with a small molecule inhibitor targeting Bcl-2 BH3 domain interactions
ComponentsApoptosis regulator Bcl-2, Bcl-2-like protein 1 chimera
KeywordsAPOPTOSIS/INHIBITOR / protein-protein interaction / alpha helical / pro-apoptosis / cytochrome c release / caspase activation / BIM / BAK / BAD / PUMA / APOPTOSIS-INHIBITOR complex
Function / homology
Function and homology information


negative regulation of cellular pH reduction / negative regulation of retinal cell programmed cell death / pigment granule organization / channel inhibitor activity / CD8-positive, alpha-beta T cell lineage commitment / BAD-BCL-2 complex / regulation of glycoprotein biosynthetic process / melanin metabolic process / positive regulation of skeletal muscle fiber development / positive regulation of melanocyte differentiation ...negative regulation of cellular pH reduction / negative regulation of retinal cell programmed cell death / pigment granule organization / channel inhibitor activity / CD8-positive, alpha-beta T cell lineage commitment / BAD-BCL-2 complex / regulation of glycoprotein biosynthetic process / melanin metabolic process / positive regulation of skeletal muscle fiber development / positive regulation of melanocyte differentiation / myeloid cell apoptotic process / osteoblast proliferation / cochlear nucleus development / mesenchymal cell development / retinal cell programmed cell death / positive regulation of neuron maturation / negative regulation of osteoblast proliferation / gland morphogenesis / renal system process / apoptotic process in bone marrow cell / regulation of cell-matrix adhesion / T cell apoptotic process / stem cell development / negative regulation of calcium ion transport into cytosol / The NLRP1 inflammasome / SARS-CoV-1-mediated effects on programmed cell death / dendritic cell apoptotic process / melanocyte differentiation / ear development / lymphoid progenitor cell differentiation / dendritic cell proliferation / positive regulation of mononuclear cell proliferation / negative regulation of myeloid cell apoptotic process / negative regulation of epithelial cell apoptotic process / regulation of nitrogen utilization / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / glomerulus development / B cell apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / negative regulation of T cell apoptotic process / negative regulation of dendritic cell apoptotic process / oocyte development / negative regulation of execution phase of apoptosis / positive regulation of multicellular organism growth / neuron maturation / metanephros development / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / regulation of viral genome replication / negative regulation of motor neuron apoptotic process / focal adhesion assembly / endoplasmic reticulum calcium ion homeostasis / fertilization / negative regulation of B cell apoptotic process / negative regulation of ossification / response to UV-B / response to iron ion / regulation of mitochondrial membrane permeability / negative regulation of protein localization to plasma membrane / regulation of growth / calcium ion transport into cytosol / negative regulation of mitochondrial depolarization / motor neuron apoptotic process / channel activity / axon regeneration / Bcl-2 family protein complex / epithelial cell apoptotic process / smooth muscle cell migration / intrinsic apoptotic signaling pathway in response to oxidative stress / NFE2L2 regulating tumorigenic genes / organ growth / response to cycloheximide / digestive tract morphogenesis / : / branching involved in ureteric bud morphogenesis / hair follicle morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / B cell lineage commitment / cellular response to alkaloid / STAT5 activation downstream of FLT3 ITD mutants / hepatocyte apoptotic process / positive regulation of smooth muscle cell migration / B cell proliferation / pore complex / negative regulation of reproductive process / negative regulation of developmental process / negative regulation of release of cytochrome c from mitochondria / BH3 domain binding / T cell homeostasis / germ cell development / apoptotic mitochondrial changes / regulation of calcium ion transport / B cell homeostasis / negative regulation of apoptotic signaling pathway / humoral immune response / negative regulation of anoikis / extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
Similarity search - Function
Apoptosis regulator, Bcl-2 / 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 / 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-1E9 / Apoptosis regulator Bcl-2 / Bcl-2-like protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsXie, X. / Kulathila, R.
CitationJournal: ACS Med Chem Lett / Year: 2013
Title: The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.
Authors: Toure, B.B. / Miller-Moslin, K. / Yusuff, N. / Perez, L. / Dore, M. / Joud, C. / Michael, W. / DiPietro, L. / van der Plas, S. / McEwan, M. / Lenoir, F. / Hoe, M. / Karki, R. / Springer, C. ...Authors: Toure, B.B. / Miller-Moslin, K. / Yusuff, N. / Perez, L. / Dore, M. / Joud, C. / Michael, W. / DiPietro, L. / van der Plas, S. / McEwan, M. / Lenoir, F. / Hoe, M. / Karki, R. / Springer, C. / Sullivan, J. / Levine, K. / Fiorilla, C. / Xie, X. / Kulathila, R. / Herlihy, K. / Porter, D. / Visser, M.
History
DepositionDec 13, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 10, 2013Provider: repository / Type: Initial release
Revision 1.1Sep 24, 2014Group: Database references
Revision 1.2Jul 26, 2017Group: Refinement description / Source and taxonomy / Category: entity_src_gen / software
Revision 1.3Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Apoptosis regulator Bcl-2, Bcl-2-like protein 1 chimera
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,5142
Polymers19,6401
Non-polymers8741
Water3,315184
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)73.529, 73.529, 96.205
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212

-
Components

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


Mass: 19639.832 Da / Num. of mol.: 1 / Fragment: SEE REMARK 999
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BCL2, BCL2L, BCL2L1, BCLX / Production host: Escherichia coli (E. coli) / References: UniProt: P10415, UniProt: Q07817
#2: Chemical ChemComp-1E9 / N-(6-{4-[(4'-chlorobiphenyl-2-yl)methyl]piperazin-1-yl}-1,1-dioxido-1,2-benzothiazol-3-yl)-4-{[(2R)-4-(dimethylamino)-1-(phenylsulfanyl)butan-2-yl]amino}-3-nitrobenzenesulfonamide


Mass: 874.490 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C42H44ClN7O6S3
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 184 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsPROTEIN IS A CHIMERA COMPRISING RESIDUES 1-34 OF BCL-2 (UNP P10415), RESIDUES 29-44 OF BCL-X (UNP ...PROTEIN IS A CHIMERA COMPRISING RESIDUES 1-34 OF BCL-2 (UNP P10415), RESIDUES 29-44 OF BCL-X (UNP Q07817), AND RESIDUES 92-207 OF BCL-2 (UNP P10415).

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.31 Å3/Da / Density % sol: 62.84 %
Crystal growTemperature: 277 K / Method: vapor diffusion / pH: 8.6
Details: 0.05 M succinic acid, 0.25 M sodium malonate, 12% PEG3350, 0.1 M Tris-HCl, pH 8.6, VAPOR DIFFUSION, temperature 277.0K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 9, 2009
RadiationMonochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.1→48.1 Å / Num. obs: 15960 / % possible obs: 99.8 % / Observed criterion σ(I): -3 / Redundancy: 7.1 % / Biso Wilson estimate: 32.1 Å2 / Rsym value: 0.094 / Net I/σ(I): 15.1
Reflection shellResolution: 2.1→2.15 Å / Redundancy: 7.1 % / Mean I/σ(I) obs: 3.9 / Num. unique all: 558 / Rsym value: 0.468 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
PHASESphasing
PHENIX(phenix.refine)refinement
XDSdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.1→45.74 Å / SU ML: 0.23 / Phase error: 19.49 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2183 798 5 %RANDOM
Rwork0.1787 ---
all0.1807 15959 --
obs0.1807 15959 99.79 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 46.182 Å2 / ksol: 0.321 e/Å3
Displacement parameters
Baniso -1Baniso -2Baniso -3
1--3.7199 Å2-0 Å20 Å2
2---3.7199 Å2-0 Å2
3---7.4398 Å2
Refinement stepCycle: LAST / Resolution: 2.1→45.74 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1157 0 59 184 1400
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0061261
X-RAY DIFFRACTIONf_angle_d0.981713
X-RAY DIFFRACTIONf_dihedral_angle_d22.356442
X-RAY DIFFRACTIONf_chiral_restr0.061168
X-RAY DIFFRACTIONf_plane_restr0.006216
LS refinement shell

Refine-ID: X-RAY DIFFRACTION

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection obs% reflection obs (%)
2.1-2.23160.25281290.201824542454100
2.2316-2.40390.26381300.180324822482100
2.4039-2.64580.21131320.17524942494100
2.6458-3.02850.18931320.17425122512100
3.0285-3.81540.18761340.157925442544100
3.8154-45.75120.23181410.1842675267599

+
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