[English] 日本語
Yorodumi
- PDB-2w3l: Crystal Structure of Chimaeric Bcl2-xL and Phenyl Tetrahydroisoqu... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2w3l
TitleCrystal Structure of Chimaeric Bcl2-xL and Phenyl Tetrahydroisoquinoline Amide Complex
ComponentsAPOPTOSIS REGULATOR BCL-2
KeywordsAPOPTOSIS
Function / homology
Function and homology information


: / channel inhibitor activity / The NLRP1 inflammasome / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / hair follicle morphogenesis / pigmentation / regulation of viral genome replication / endoplasmic reticulum calcium ion homeostasis / Regulation of MITF-M-dependent genes involved in apoptosis / B cell proliferation ...: / channel inhibitor activity / The NLRP1 inflammasome / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / hair follicle morphogenesis / pigmentation / regulation of viral genome replication / endoplasmic reticulum calcium ion homeostasis / Regulation of MITF-M-dependent genes involved in apoptosis / B cell proliferation / regulation of mitochondrial membrane permeability / response to iron ion / negative regulation of mitochondrial depolarization / Bcl-2 family protein complex / NFE2L2 regulating tumorigenic genes / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of intrinsic apoptotic signaling pathway / humoral immune response / pore complex / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / negative regulation of anoikis / extrinsic apoptotic signaling pathway in absence of ligand / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / BH3 domain binding / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / Activation of BAD and translocation to mitochondria / positive regulation of B cell proliferation / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / neuron apoptotic process / release of cytochrome c from mitochondria / response to cytokine / B cell receptor signaling pathway / negative regulation of autophagy / regulation of mitochondrial membrane potential / protein phosphatase 2A binding / intrinsic apoptotic signaling pathway in response to DNA damage / response to nicotine / female pregnancy / myelin sheath / response to radiation / response to toxic substance / autophagy / protein polyubiquitination / positive regulation of cell growth / negative regulation of neuron apoptotic process / nuclear membrane / channel activity / protease binding / Interleukin-4 and Interleukin-13 signaling / DNA-binding transcription factor binding / defense response to virus / Estrogen-dependent gene expression / sequence-specific DNA binding / molecular adaptor activity / mitochondrial outer membrane / response to xenobiotic stimulus / positive regulation of apoptotic process / protein heterodimerization activity / ubiquitin protein ligase binding / apoptotic process / positive regulation of cell population proliferation / negative regulation of apoptotic process / DNA damage response / endoplasmic reticulum membrane / endoplasmic reticulum / protein-containing complex / mitochondrion / membrane / identical protein binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Apoptosis regulator, Bcl-2 / 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 / Blc2-like / Apoptosis Regulator Bcl-x ...Apoptosis regulator, Bcl-2 / 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 / Blc2-like / Apoptosis Regulator Bcl-x / 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-2 family / BCL (B-Cell lymphoma); contains BH1, BH2 regions / Bcl2-like / Bcl-2, Bcl-2 homology region 1-3 / Apoptosis regulator proteins, Bcl-2 family / BCL2-like apoptosis inhibitors family profile. / Bcl-2-like superfamily / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-DRO / Apoptosis regulator Bcl-2
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsPorter, J. / Payne, A. / de Candole, B. / Ford, D. / Hutchinson, B. / Trevitt, G. / Turner, J. / Edwards, C. / Watkins, C. / Whitcombe, I. ...Porter, J. / Payne, A. / de Candole, B. / Ford, D. / Hutchinson, B. / Trevitt, G. / Turner, J. / Edwards, C. / Watkins, C. / Whitcombe, I. / Davis, J. / Stubberfield, C. / Fisher, M. / Lamers, M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2009
Title: Tetrahydroisoquinoline Amide Substituted Phenyl Pyrazoles as Selective Bcl-2 Inhibitors.
Authors: Porter, J. / Payne, A. / De Candole, B. / Ford, D. / Hutchinson, B. / Trevitt, G. / Turner, J. / Edwards, C. / Watkins, C. / Whitcombe, I. / Davis, J. / Stubberfield, C.
History
DepositionNov 13, 2008Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 9, 2008Provider: repository / Type: Initial release
Revision 1.1May 8, 2011Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Jun 28, 2017Group: Data collection / Category: diffrn_source / Item: _diffrn_source.type
Revision 1.4May 8, 2024Group: Data collection / Database references / Other
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: APOPTOSIS REGULATOR BCL-2
B: APOPTOSIS REGULATOR BCL-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,9024
Polymers33,7502
Non-polymers1,1522
Water4,017223
1
A: APOPTOSIS REGULATOR BCL-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)17,4512
Polymers16,8751
Non-polymers5761
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPQS
2
B: APOPTOSIS REGULATOR BCL-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)17,4512
Polymers16,8751
Non-polymers5761
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPQS
Unit cell
Length a, b, c (Å)68.000, 68.320, 70.670
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein APOPTOSIS REGULATOR BCL-2 / BCL2-XL


Mass: 16874.928 Da / Num. of mol.: 2 / Fragment: RESIDUES 9-33,92-206
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P10415
#2: Chemical ChemComp-DRO / 1-(2-{[(3S)-3-(aminomethyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}phenyl)-4-chloro-5-methyl-N,N-diphenyl-1H-pyrazole-3-carboxamide


Mass: 576.087 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H30ClN5O2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 223 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsTHE AUTHORS SUGGEST THE FLEXIBLE LOOP BETWEEN N- AND C-TERMINUS IS A CHIMERA

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.23 Å3/Da / Density % sol: 44.5 % / Description: NONE

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54
DetectorType: RIGAKU (RAXIS4) / Detector: IMAGE PLATE / Date: Mar 13, 2006 / Details: VARIMAX-HF
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.1→19.91 Å / Num. obs: 22774 / % possible obs: 99.8 % / Observed criterion σ(I): 0.01 / Redundancy: 6.97 % / Rmerge(I) obs: 0.1 / Net I/σ(I): 8.4

-
Processing

SoftwareName: REFMAC / Version: 5.2.0019 / Classification: refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.1→20 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.921 / SU B: 5.425 / SU ML: 0.149 / Cross valid method: THROUGHOUT / ESU R: 0.261 / ESU R Free: 0.21 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
RfactorNum. reflection% reflectionSelection details
Rfree0.258 1012 5.1 %RANDOM
Rwork0.218 ---
obs0.218 18688 99.6 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 28.3 Å2
Baniso -1Baniso -2Baniso -3
1-2.91 Å20 Å20 Å2
2---1.96 Å20 Å2
3----0.95 Å2
Refinement stepCycle: LAST / Resolution: 2.1→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2318 0 84 223 2625
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0180.0212476
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.7181.9513357
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3955279
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.18722.632133
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.50115370
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.9331523
X-RAY DIFFRACTIONr_chiral_restr0.1180.2327
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.021987
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.2130.31204
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.3160.51702
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.2420.5263
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2040.368
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.2570.530
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.2531.51435
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.97622224
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it3.09531234
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it4.7984.51133
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.1→2.15 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.303 71
Rwork0.235 1340

+
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