[English] 日本語
Yorodumi
- PDB-9git: BFL1 covalently bound to inhibitor compound 43 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9git
TitleBFL1 covalently bound to inhibitor compound 43
ComponentsBcl-2-related protein A1
KeywordsAPOPTOSIS / BFL / BCL / covalent / inhibitor
Function / homology
Function and homology information


Regulation of MITF-M-dependent genes involved in apoptosis / mitochondrial fusion / Nuclear events stimulated by ALK signaling in cancer / extrinsic apoptotic signaling pathway in absence of ligand / release of cytochrome c from mitochondria / intrinsic apoptotic signaling pathway in response to DNA damage / channel activity / mitochondrial outer membrane / positive regulation of apoptotic process / negative regulation of apoptotic process ...Regulation of MITF-M-dependent genes involved in apoptosis / mitochondrial fusion / Nuclear events stimulated by ALK signaling in cancer / extrinsic apoptotic signaling pathway in absence of ligand / release of cytochrome c from mitochondria / intrinsic apoptotic signaling pathway in response to DNA damage / channel activity / mitochondrial outer membrane / positive regulation of apoptotic process / negative regulation of apoptotic process / cytosol / cytoplasm
Similarity search - Function
Bcl-2-related protein A1 / 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 ...Bcl-2-related protein A1 / 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
Similarity search - Domain/homology
: / Bcl-2-related protein A1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.145 Å
AuthorsCottee, M.A.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Other private United Kingdom
CitationJournal: J.Med.Chem. / Year: 2024
Title: Structure-Based Discovery of a Series of Covalent, Orally Bioavailable, and Selective BFL1 Inhibitors.
Authors: Palisse, A. / Cheung, T. / Blokhuis, A. / Cogswell, T. / Martins, B.S. / Riemens, R. / Schellekens, R. / Battocchio, G. / Jansen, C. / Cottee, M.A. / Ornell, K. / Sacchetto, C. / Leon, L. / ...Authors: Palisse, A. / Cheung, T. / Blokhuis, A. / Cogswell, T. / Martins, B.S. / Riemens, R. / Schellekens, R. / Battocchio, G. / Jansen, C. / Cottee, M.A. / Ornell, K. / Sacchetto, C. / Leon, L. / van Hoek-Emmelot, M. / Bostock, M. / Brauer, B.L. / Beaumont, K. / Lucas, S.C.C. / Ahmed, S. / Blackwell, J.H. / Borjesson, U. / Gohlke, A. / Gramatikov, I.M.T. / Hargreaves, D. / van Hoeven, V. / Kantae, V. / Kupcova, L. / Milbradt, A.G. / Seneviratne, U. / Su, N. / Vales, J. / Wang, H. / White, M.J. / Kinzel, O.
History
DepositionAug 19, 2024Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 18, 2024Provider: repository / Type: Initial release
Revision 1.1Jan 8, 2025Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bcl-2-related protein A1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)18,0522
Polymers17,4431
Non-polymers6091
Water1,71195
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area8030 Å2
Unit cell
Length a, b, c (Å)40.329, 42.854, 43.138
Angle α, β, γ (deg.)90, 101.02, 90
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Bcl-2-related protein A1 / Bcl-2-like protein 5 / Bcl2-L-5 / Hemopoietic-specific early response protein / Protein BFL-1 / Protein GRS


Mass: 17442.889 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BCL2A1, BCL2L5, BFL1, GRS, HBPA1 / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: Q16548
#2: Chemical ChemComp-A1ILW / (3~{S})-3-[[4-[(1~{R},3~{R})-3-[[(3~{R})-1,1-bis(oxidanylidene)thiolan-3-yl]carbamoylamino]cyclopentyl]oxy-3-fluoranyl-phenyl]-propanoyl-amino]-3-(4-chlorophenyl)propanamide


Mass: 609.109 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H34ClFN4O6S / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 95 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.14 Å3/Da / Density % sol: 42.63 % / Description: Thick pointed rods/plates
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.14
Details: Protein:ligand complex at ~4mg/ml in 20 mM HEPES pH 7.5, 150 mM NaCl, 5% glycerol, 2 mM TCEP, 1%DMSO. 150nL mixed with 150nL of well solution, 0.1M PCPT* pH 7.14, Na3 Citrate 0.92 M. *PCPT = ...Details: Protein:ligand complex at ~4mg/ml in 20 mM HEPES pH 7.5, 150 mM NaCl, 5% glycerol, 2 mM TCEP, 1%DMSO. 150nL mixed with 150nL of well solution, 0.1M PCPT* pH 7.14, Na3 Citrate 0.92 M. *PCPT = Sodium propionate, sodium cacodylate trihydrate, bis-tris propane buffer system. Using STPLabtech Mosquito.

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.95374 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Sep 18, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.95374 Å / Relative weight: 1
ReflectionResolution: 1.145→32.143 Å / Num. obs: 39710 / % possible obs: 76.3 % / Redundancy: 4.9 % / CC1/2: 0.998 / Rmerge(I) obs: 0.041 / Rpim(I) all: 0.02 / Rrim(I) all: 0.046 / Net I/σ(I): 12.6
Reflection shellResolution: 1.145→1.252 Å / Redundancy: 2.5 % / Rmerge(I) obs: 0.496 / Mean I/σ(I) obs: 1.4 / Num. unique obs: 1985 / CC1/2: 0.723 / Rpim(I) all: 0.37 / Rrim(I) all: 0.622 / % possible all: 16.4

-
Processing

Software
NameVersionClassification
BUSTER2.11.8refinement
XDSJun 30, 2023data reduction
Aimless0.7.13data scaling
autoPROC1.0.5 (20230726)data processing
STARANISO2.3.94 (20230525)data scaling
PHASERCCP4 8.0.004phasing
Coot0.9.8.83model building
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.145→16.66 Å / Cor.coef. Fo:Fc: 0.959 / Cor.coef. Fo:Fc free: 0.948 / SU R Cruickshank DPI: 0.047 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.047 / SU Rfree Blow DPI: 0.049 / SU Rfree Cruickshank DPI: 0.049
RfactorNum. reflection% reflectionSelection details
Rfree0.2116 1922 -RANDOM
Rwork0.1906 ---
obs0.1916 39691 76.2 %-
Displacement parametersBiso mean: 17.72 Å2
Baniso -1Baniso -2Baniso -3
1-0.2556 Å20 Å20.0537 Å2
2---0.0921 Å20 Å2
3----0.1635 Å2
Refine analyzeLuzzati coordinate error obs: 0.15 Å
Refinement stepCycle: LAST / Resolution: 1.145→16.66 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1179 0 41 95 1315
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0131272HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.21736HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d451SINUSOIDAL2
X-RAY DIFFRACTIONt_gen_planes231HARMONIC5
X-RAY DIFFRACTIONt_it1272HARMONIC10
X-RAY DIFFRACTIONt_chiral_improper_torsion164SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact1367SEMIHARMONIC4
X-RAY DIFFRACTIONt_omega_torsion3.96
X-RAY DIFFRACTIONt_other_torsion12.69
LS refinement shellResolution: 1.15→1.22 Å
RfactorNum. reflection% reflection
Rfree0.2497 38 -
Rwork0.2656 --
obs0.2649 794 8.82 %
Refinement TLS params.Origin x: 12.1256 Å / Origin y: 0.015 Å / Origin z: 7.9025 Å
111213212223313233
T-0.0102 Å2-0.0139 Å20.0027 Å2--0.0184 Å20.0021 Å2---0.0222 Å2
L0.6203 °2-0.3076 °20.0276 °2-0.9994 °2-0.0569 °2--0.5905 °2
S0.0169 Å °0.0257 Å °0.0252 Å °0.0257 Å °-0.0094 Å °-0.0259 Å °0.0252 Å °-0.0259 Å °-0.0074 Å °
Refinement TLS groupSelection details: { A|* }

+
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