[English] 日本語
Yorodumi
- PDB-8vxm: Human Bcl-2/Bcl-xL Chimera Fused to MBP in Complex with Inhibitor... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8vxm
TitleHuman Bcl-2/Bcl-xL Chimera Fused to MBP in Complex with Inhibitor S55746
ComponentsMaltose/maltodextrin-binding periplasmic protein fused to apoptosis regulator Bcl-2/Bcl-xL chimera
KeywordsAPOPTOSIS / Bcl-2 / MBP Fusion / Bcl-xL Chimera / S55746 / Complex / Protein-Protein Interface Inhibitor
Function / homology
Function and homology information


channel inhibitor activity / negative regulation of cellular pH reduction / negative regulation of retinal cell programmed cell death / pigment granule organization / CD8-positive, alpha-beta T cell lineage commitment / BAD-BCL-2 complex / positive regulation of skeletal muscle fiber development / regulation of glycoprotein biosynthetic process / positive regulation of melanocyte differentiation / melanin metabolic process ...channel inhibitor activity / negative regulation of cellular pH reduction / negative regulation of retinal cell programmed cell death / pigment granule organization / CD8-positive, alpha-beta T cell lineage commitment / BAD-BCL-2 complex / positive regulation of skeletal muscle fiber development / regulation of glycoprotein biosynthetic process / positive regulation of melanocyte differentiation / melanin metabolic process / myeloid cell apoptotic process / cochlear nucleus development / osteoblast proliferation / mesenchymal cell development / retinal cell programmed cell death / positive regulation of neuron maturation / negative regulation of osteoblast proliferation / gland morphogenesis / apoptotic process in bone marrow cell / renal system process / regulation of cell-matrix adhesion / The NLRP1 inflammasome / dendritic cell apoptotic process / ear development / negative regulation of calcium ion transport into cytosol / SARS-CoV-1-mediated effects on programmed cell death / stem cell development / dendritic cell proliferation / lymphoid progenitor cell differentiation / positive regulation of mononuclear cell proliferation / T cell apoptotic process / melanocyte differentiation / negative regulation of myeloid cell apoptotic process / negative regulation of epithelial cell apoptotic process / BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members / negative regulation of dendritic cell apoptotic process / B cell apoptotic process / regulation of nitrogen utilization / negative regulation of T cell apoptotic process / glomerulus development / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of multicellular organism growth / metanephros development / Regulation of MITF-M-dependent genes involved in apoptosis / neuron maturation / focal adhesion assembly / negative regulation of motor neuron apoptotic process / regulation of viral genome replication / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / oocyte development / negative regulation of execution phase of apoptosis / endoplasmic reticulum calcium ion homeostasis / fertilization / regulation of growth / regulation of mitochondrial membrane permeability / calcium ion transport into cytosol / response to UV-B / response to iron ion / negative regulation of ossification / motor neuron apoptotic process / negative regulation of mitochondrial depolarization / axon regeneration / epithelial cell apoptotic process / Bcl-2 family protein complex / smooth muscle cell migration / NFE2L2 regulating tumorigenic genes / intrinsic apoptotic signaling pathway in response to oxidative stress / organ growth / negative regulation of B cell apoptotic process / hair follicle morphogenesis / branching involved in ureteric bud morphogenesis / apoptotic mitochondrial changes / digestive tract morphogenesis / response to cycloheximide / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / STAT5 activation downstream of FLT3 ITD mutants / B cell lineage commitment / cellular response to alkaloid / positive regulation of smooth muscle cell migration / negative regulation of G1/S transition of mitotic cell cycle / hepatocyte apoptotic process / pore complex / detection of maltose stimulus / negative regulation of release of cytochrome c from mitochondria / maltose transport complex / negative regulation of reproductive process / negative regulation of developmental process / negative regulation of intrinsic apoptotic signaling pathway / T cell homeostasis / germ cell development / carbohydrate transport / BH3 domain binding / B cell homeostasis / humoral immune response / B cell proliferation / negative regulation of apoptotic signaling pathway / negative regulation of anoikis / regulation of calcium ion transport / extrinsic apoptotic signaling pathway via death domain receptors / 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-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 / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein
Similarity search - Domain/homology
Chem-F3Q / DI(HYDROXYETHYL)ETHER / Maltose/maltodextrin-binding periplasmic protein / Apoptosis regulator Bcl-2 / Bcl-2-like protein 1
Similarity search - Component
Biological speciesEscherichia coli K-12 (bacteria)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsBaird, J. / Holliday, M.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Anal.Chem. / Year: 2025
Title: Hydrogen/Deuterium Exchange and Protein Oxidative Footprinting with Mass Spectrometry Collectively Discriminate the Binding of Small-Molecule Therapeutics to Bcl-2.
Authors: Sun, Y. / Houde, D. / Iacob, R.E. / Baird, J. / Swift, R.V. / Holliday, M. / Shi, X. / Sidoli, S. / Brenowitz, M.
History
DepositionFeb 5, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 2, 2024Provider: repository / Type: Initial release
Revision 1.1Mar 5, 2025Group: Database references / Structure summary / Category: citation / citation_author / pdbx_entry_details
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _pdbx_entry_details.has_protein_modification
Revision 1.2Mar 12, 2025Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Maltose/maltodextrin-binding periplasmic protein fused to apoptosis regulator Bcl-2/Bcl-xL chimera
hetero molecules


Theoretical massNumber of molelcules
Total (without water)62,0783
Polymers61,2611
Non-polymers8172
Water1,22568
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)48.800, 88.740, 134.910
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#1: Protein Maltose/maltodextrin-binding periplasmic protein fused to apoptosis regulator Bcl-2/Bcl-xL chimera / Bcl2-L-1 / Apoptosis regulator Bcl-X


Mass: 61260.816 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: For the alignment, MBP (UNP P0AEX9, 27-392) spans residues 19-384 (w/ surface entropy reduction mutations at 100, 101, 190, 191, and 257) and is fused to a Bcl-2/Bcl-xL chimera via a linker ...Details: For the alignment, MBP (UNP P0AEX9, 27-392) spans residues 19-384 (w/ surface entropy reduction mutations at 100, 101, 190, 191, and 257) and is fused to a Bcl-2/Bcl-xL chimera via a linker sequence (AARAAA) spanning 385-390. Bcl-2 (UNP P10415, 10-207) has the unstructured loop spanning 35-91 deleted and replaced with Bcl-xL (UNP Q07817, 29-44) for residues 35-50 of the Bcl-2/Bcl-xL chimera, so Bcl-2 spans 391-415 and 432-547, while Bcl-xL spans 416-431. For the 3D model, MBP (-362-3), linker (4-9), Bcl-2 (10-34 and 92-207), and Bcl-xL (35-50). THR88, GLU89, SER90, and GLU91 of the final model correspond to residues 47-50 (Bcl-xL) of the loop replacement (35-50).
Source: (gene. exp.) Escherichia coli K-12 (bacteria), (gene. exp.) Homo sapiens (human)
Strain: K-12 / Gene: malE, b4034, JW3994, BCL2, BCL2L1, BCL2L, BCLX / Plasmid: pET-24b(+) / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P0AEX9, UniProt: P10415, UniProt: Q07817
#2: Chemical ChemComp-F3Q / ~{N}-(4-hydroxyphenyl)-3-[6-[[(3~{S})-3-(morpholin-4-ylmethyl)-3,4-dihydro-1~{H}-isoquinolin-2-yl]carbonyl]-1,3-benzodioxol-5-yl]-~{N}-phenyl-5,6,7,8-tetrahydroindolizine-1-carboxamide


Mass: 710.817 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C43H42N4O6 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 68 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.38 Å3/Da / Density % sol: 48.41 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 100 mM Tris (pH 8.5), 25% PEG 3350, 200 mM lithium sulfate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Apr 15, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.035→67.455 Å / Num. obs: 35939 / % possible obs: 93.5 % / Redundancy: 6.6 % / Biso Wilson estimate: 44.02 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.054 / Rpim(I) all: 0.023 / Rrim(I) all: 0.059 / Net I/σ(I): 16.1
Reflection shellResolution: 2.035→2.07 Å / Redundancy: 5.6 % / Rmerge(I) obs: 0.844 / Mean I/σ(I) obs: 1.8 / Num. unique obs: 1390 / CC1/2: 0.855 / Rpim(I) all: 0.382 / Rrim(I) all: 0.93

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
autoPROC1.1.7data reduction
PHASERphasing
autoPROCdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.1→67.45 Å / SU ML: 0.322 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 31.0819
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2433 1694 5.03 %
Rwork0.2185 31979 -
obs0.2198 33673 96.09 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 55.97 Å2
Refinement stepCycle: LAST / Resolution: 2.1→67.45 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4051 0 60 68 4179
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00154219
X-RAY DIFFRACTIONf_angle_d0.40535727
X-RAY DIFFRACTIONf_chiral_restr0.0369603
X-RAY DIFFRACTIONf_plane_restr0.0038755
X-RAY DIFFRACTIONf_dihedral_angle_d21.09691563
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.1-2.160.3531530.30792705X-RAY DIFFRACTION99.31
2.16-2.230.34061460.29362705X-RAY DIFFRACTION99.41
2.23-2.310.35931040.26982300X-RAY DIFFRACTION83.39
2.31-2.40.31211400.27512718X-RAY DIFFRACTION99.44
2.4-2.510.32531420.25962712X-RAY DIFFRACTION99.51
2.51-2.650.30831520.25392717X-RAY DIFFRACTION99.17
2.65-2.810.27681040.26312053X-RAY DIFFRACTION74
2.81-3.030.29211640.28112714X-RAY DIFFRACTION99.65
3.03-3.330.26081330.26182784X-RAY DIFFRACTION99.83
3.33-3.820.25141430.21232795X-RAY DIFFRACTION99.86
3.82-4.810.21261580.17252818X-RAY DIFFRACTION99.7
4.81-67.450.18311550.18112958X-RAY DIFFRACTION99.52
Refinement TLS params.Method: refined / Origin x: -8.47160108725 Å / Origin y: 7.50239497536 Å / Origin z: -16.326501899 Å
111213212223313233
T0.528722311606 Å2-0.0391870850931 Å2-0.00710673473376 Å2-0.274775055359 Å2-0.0176923176091 Å2--0.547358419366 Å2
L0.517844861461 °2-0.175723519671 °20.0218443906523 °2-1.95166089648 °2-0.746166512851 °2--1.21102067192 °2
S-0.0162669397629 Å °0.0449191822317 Å °-0.00132374469137 Å °-0.253696846085 Å °-0.0477923476229 Å °0.0137874814489 Å °0.150796968811 Å °-0.00906996552643 Å °0.0514168139465 Å °
Refinement TLS groupSelection details: all

+
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