[English] 日本語
Yorodumi
- PDB-4lxd: Bcl_2-Navitoclax Analog (without Thiophenyl) Complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4lxd
TitleBcl_2-Navitoclax Analog (without Thiophenyl) Complex
ComponentsApoptosis regulator Bcl-2
KeywordsAPOPTOSIS REGULATOR/INHIBITOR / 8 helices / APOPTOSIS REGULATOR-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 / positive regulation of skeletal muscle fiber development / melanin metabolic process / 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 / positive regulation of skeletal muscle fiber development / melanin metabolic process / positive regulation of melanocyte differentiation / myeloid cell apoptotic process / gland morphogenesis / cochlear nucleus development / osteoblast proliferation / mesenchymal cell development / retinal cell programmed cell death / positive regulation of neuron maturation / negative regulation of osteoblast proliferation / ear development / renal system process / regulation of cell-matrix adhesion / stem cell development / negative regulation of calcium ion transport into cytosol / The NLRP1 inflammasome / dendritic cell apoptotic process / lymphoid progenitor cell differentiation / melanocyte differentiation / T cell apoptotic process / B cell apoptotic process / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / negative regulation of myeloid cell apoptotic process / negative regulation of epithelial cell apoptotic process / negative regulation of T cell apoptotic process / negative regulation of dendritic cell apoptotic process / glomerulus development / regulation of nitrogen utilization / endoplasmic reticulum calcium ion homeostasis / oocyte development / Regulation of MITF-M-dependent genes involved in apoptosis / neuron maturation / positive regulation of multicellular organism growth / metanephros development / regulation of viral genome replication / negative regulation of motor neuron apoptotic process / focal adhesion assembly / regulation of mitochondrial membrane permeability / negative regulation of ossification / calcium ion transport into cytosol / negative regulation of B cell apoptotic process / response to UV-B / response to iron ion / motor neuron apoptotic process / negative regulation of mitochondrial depolarization / BH domain binding / organ growth / axon regeneration / epithelial cell apoptotic process / smooth muscle cell migration / hair follicle morphogenesis / B cell lineage commitment / NFE2L2 regulating tumorigenic genes / intrinsic apoptotic signaling pathway in response to oxidative stress / branching involved in ureteric bud morphogenesis / digestive tract morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / pore complex / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of smooth muscle cell migration / B cell proliferation / T cell homeostasis / B cell homeostasis / BH3 domain binding / regulation of calcium ion transport / humoral immune response / negative regulation of apoptotic signaling pathway / negative regulation of anoikis / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / behavioral fear response / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / extrinsic apoptotic signaling pathway via death domain receptors / Activation of BAD and translocation to mitochondria / hematopoietic stem cell differentiation / negative regulation of reactive oxygen species metabolic process / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / negative regulation of intrinsic apoptotic signaling pathway / cellular response to glucose starvation / skeletal muscle fiber development / extrinsic apoptotic signaling pathway in absence of ligand / response to glucocorticoid / ovarian follicle development / spleen development / positive regulation of B cell proliferation / homeostasis of number of cells within a tissue / post-embryonic development / axonogenesis / ossification / release of cytochrome c from mitochondria / negative regulation of autophagy / reactive oxygen species metabolic process / response to cytokine
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 / Apoptosis regulator, Bcl-2, BH3 motif, conserved site / Apoptosis regulator, Bcl-2 family BH3 motif signature. ...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 / 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 / BCL2-like apoptosis inhibitors family profile. / Apoptosis regulator proteins, Bcl-2 family / Bcl-2-like superfamily
Similarity search - Domain/homology
Chem-1XV / Apoptosis regulator Bcl-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsPark, C.H.
CitationJournal: NAT.MED. (N.Y.) / Year: 2013
Title: ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.
Authors: Souers, A.J. / Leverson, J.D. / Boghaert, E.R. / Ackler, S.L. / Catron, N.D. / Chen, J. / Dayton, B.D. / Ding, H. / Enschede, S.H. / Fairbrother, W.J. / Huang, D.C. / Hymowitz, S.G. / Jin, S. ...Authors: Souers, A.J. / Leverson, J.D. / Boghaert, E.R. / Ackler, S.L. / Catron, N.D. / Chen, J. / Dayton, B.D. / Ding, H. / Enschede, S.H. / Fairbrother, W.J. / Huang, D.C. / Hymowitz, S.G. / Jin, S. / Khaw, S.L. / Kovar, P.J. / Lam, L.T. / Lee, J. / Maecker, H.L. / Marsh, K.C. / Mason, K.D. / Mitten, M.J. / Nimmer, P.M. / Oleksijew, A. / Park, C.H. / Park, C.M. / Phillips, D.C. / Roberts, A.W. / Sampath, D. / Seymour, J.F. / Smith, M.L. / Sullivan, G.M. / Tahir, S.K. / Tse, C. / Wendt, M.D. / Xiao, Y. / Xue, J.C. / Zhang, H. / Humerickhouse, R.A. / Rosenberg, S.H. / Elmore, S.W.
History
DepositionJul 29, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 14, 2013Provider: repository / Type: Initial release
Revision 1.1Aug 2, 2017Group: Refinement description / Source and taxonomy / Category: entity_src_gen / software
Revision 1.2Feb 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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,0802
Polymers19,3841
Non-polymers6961
Water4,161231
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)86.515, 86.515, 62.425
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number169
Space group name H-MP61

-
Components

#1: Protein Apoptosis regulator Bcl-2


Mass: 19383.594 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 1-34, 92-207 / Mutation: A2P
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BCL2 / Production host: Escherichia coli (E. coli) / References: UniProt: P10415
#2: Chemical ChemComp-1XV / 4-(4-{[4-(4-chlorophenyl)-5,6-dihydro-2H-pyran-3-yl]methyl}piperazin-1-yl)-N-{[3-nitro-4-(tetrahydro-2H-pyran-4-ylamino)phenyl]sulfonyl}benzamide


Mass: 696.213 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H38ClN5O7S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 231 / 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: 3.48 Å3/Da / Density % sol: 64.65 %
Crystal growTemperature: 296 K / Method: vapor diffusion / pH: 6.5
Details: 1.5 M (NH4)2SO4, 0.1 M MES, 8%(V/V) PEG400, pH 6.5, VAPOR DIFFUSION, temperature 296K

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Aug 6, 2007
RadiationMonochromator: mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.9→37.46 Å / Num. all: 21056 / Num. obs: 20997 / % possible obs: 99.72 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Biso Wilson estimate: 24.93 Å2
Reflection shellResolution: 1.9→1.99 Å / Num. unique all: 2705 / % possible all: 99.72

-
Processing

Software
NameVersionClassification
ADSCQuantumdata collection
AMoREphasing
BUSTER2.11.2refinement
DENZOdata reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.9→37.46 Å / Cor.coef. Fo:Fc: 0.9434 / Cor.coef. Fo:Fc free: 0.9354 / SU R Cruickshank DPI: 0.106 / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.2124 1077 5.13 %RANDOM
Rwork0.18 ---
obs0.1816 20997 99.72 %-
all-21056 --
Displacement parametersBiso mean: 28.37 Å2
Baniso -1Baniso -2Baniso -3
1--1.2359 Å20 Å20 Å2
2---1.2359 Å20 Å2
3---2.4719 Å2
Refine analyzeLuzzati coordinate error obs: 0.185 Å
Refinement stepCycle: LAST / Resolution: 1.9→37.46 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1188 0 48 231 1467
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONo_bond_d0.011275HARMONIC2
X-RAY DIFFRACTIONo_angle_deg0.931726HARMONIC2
X-RAY DIFFRACTIONo_improper_angle_d2.97433SINUSOIDAL2
X-RAY DIFFRACTIONo_dihedral_angle_d18.230HARMONIC2
LS refinement shellResolution: 1.9→1.99 Å / Total num. of bins used: 11
RfactorNum. reflection% reflection
Rfree0.2344 154 5.69 %
Rwork0.197 2551 -
all0.1991 2705 -
obs--99.72 %

+
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