[English] 日本語
Yorodumi
- PDB-3fzl: Crystal Structures of Hsc70/Bag1 in Complex with Small Molecule I... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3fzl
TitleCrystal Structures of Hsc70/Bag1 in Complex with Small Molecule Inhibitors
Components
  • BAG family molecular chaperone regulator 1
  • Heat shock cognate 71 kDa protein
KeywordsCHAPERONE / HSP70 / HSC70 / BAG1 / heat shock / protein folding / adenosine / nucleotide / nucleotide exchange factor / small molecule inhibitor / ATP-binding / nucleotide-binding / stress response / apoptosis
Function / homology
Function and homology information


lumenal side of lysosomal membrane / regulation of protein import / negative regulation of supramolecular fiber organization / chaperone-mediated autophagy translocation complex disassembly / protein carrier chaperone / clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane / Respiratory syncytial virus genome transcription / Lipophagy / GABA synthesis, release, reuptake and degradation / protein targeting to lysosome involved in chaperone-mediated autophagy ...lumenal side of lysosomal membrane / regulation of protein import / negative regulation of supramolecular fiber organization / chaperone-mediated autophagy translocation complex disassembly / protein carrier chaperone / clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane / Respiratory syncytial virus genome transcription / Lipophagy / GABA synthesis, release, reuptake and degradation / protein targeting to lysosome involved in chaperone-mediated autophagy / adenyl-nucleotide exchange factor activity / clathrin coat disassembly / C3HC4-type RING finger domain binding / positive regulation of smooth muscle cell apoptotic process / negative regulation of NLRP3 inflammasome complex assembly / CHL1 interactions / regulation of protein complex stability / ATP-dependent protein disaggregase activity / membrane organization / Prp19 complex / protein folding chaperone complex / Lysosome Vesicle Biogenesis / cellular response to steroid hormone stimulus / Golgi Associated Vesicle Biogenesis / chaperone-mediated autophagy / non-chaperonin molecular chaperone ATPase / chaperone cofactor-dependent protein refolding / Regulation of HSF1-mediated heat shock response / HSF1-dependent transactivation / response to unfolded protein / regulation of protein-containing complex assembly / Attenuation phase / Protein methylation / ATP metabolic process / heat shock protein binding / protein folding chaperone / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / mRNA Splicing - Major Pathway / lysosomal lumen / cellular response to starvation / AUF1 (hnRNP D0) binds and destabilizes mRNA / spliceosomal complex / G protein-coupled receptor binding / ATP-dependent protein folding chaperone / Late endosomal microautophagy / regulation of protein stability / PKR-mediated signaling / mRNA splicing, via spliceosome / Chaperone Mediated Autophagy / MHC class II protein complex binding / unfolded protein binding / melanosome / protein folding / Clathrin-mediated endocytosis / protein-folding chaperone binding / protein refolding / protein-macromolecule adaptor activity / secretory granule lumen / Interleukin-4 and Interleukin-13 signaling / blood microparticle / ficolin-1-rich granule lumen / cell surface receptor signaling pathway / protein stabilization / positive regulation of cell migration / cadherin binding / receptor ligand activity / ribonucleoprotein complex / lysosomal membrane / focal adhesion / negative regulation of DNA-templated transcription / ubiquitin protein ligase binding / Neutrophil degranulation / apoptotic process / negative regulation of apoptotic process / nucleolus / enzyme binding / ATP hydrolysis activity / extracellular space / RNA binding / extracellular exosome / extracellular region / nucleoplasm / ATP binding / nucleus / membrane / plasma membrane / cytosol / cytoplasm
Similarity search - Function
BAG domain / Molecular chaperone regulator BAG / BAG domain superfamily / BAG domain / BAG domain / BAG domain profile. / BAG domains, present in regulator of Hsp70 proteins / Defensin A-like - #30 / Defensin A-like / Heat shock hsp70 proteins family signature 2. ...BAG domain / Molecular chaperone regulator BAG / BAG domain superfamily / BAG domain / BAG domain / BAG domain profile. / BAG domains, present in regulator of Hsp70 proteins / Defensin A-like - #30 / Defensin A-like / Heat shock hsp70 proteins family signature 2. / Heat shock hsp70 proteins family signature 1. / Heat shock hsp70 proteins family signature 3. / Heat shock protein 70, conserved site / Heat shock protein 70kD, peptide-binding domain superfamily / Heat shock protein 70 family / Hsp70 protein / Heat shock protein 70kD, C-terminal domain superfamily / ATPase, substrate binding domain, subdomain 4 / Actin; Chain A, domain 4 / ATPase, nucleotide binding domain / Methane Monooxygenase Hydroxylase; Chain G, domain 1 / ATPase, nucleotide binding domain / Ubiquitin family / Ubiquitin homologues / Nucleotidyltransferase; domain 5 / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily / Alpha-Beta Complex / Up-down Bundle / 2-Layer Sandwich / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-3FD / Heat shock cognate 71 kDa protein / BAG family molecular chaperone regulator 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsDokurno, P. / Williamson, D.S. / Murray, J.B. / Surgenor, A.E.
CitationJournal: J.Med.Chem. / Year: 2009
Title: Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design
Authors: Williamson, D.S. / Borgognoni, J. / Clay, A. / Daniels, Z. / Dokurno, P. / Drysdale, M.J. / Foloppe, N. / Francis, G.L. / Graham, C.J. / Howes, R. / Macias, A.T. / Murray, J.B. / Parsons, R. ...Authors: Williamson, D.S. / Borgognoni, J. / Clay, A. / Daniels, Z. / Dokurno, P. / Drysdale, M.J. / Foloppe, N. / Francis, G.L. / Graham, C.J. / Howes, R. / Macias, A.T. / Murray, J.B. / Parsons, R. / Shaw, T. / Surgenor, A.E. / Terry, L. / Wang, Y. / Wood, M. / Massey, A.J.
History
DepositionJan 26, 2009Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Mar 17, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Nov 1, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / 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
Revision 1.3Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Heat shock cognate 71 kDa protein
B: BAG family molecular chaperone regulator 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,9224
Polymers55,2442
Non-polymers6792
Water5,495305
1
A: Heat shock cognate 71 kDa protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,7653
Polymers42,0871
Non-polymers6792
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: BAG family molecular chaperone regulator 1


Theoretical massNumber of molelcules
Total (without water)13,1571
Polymers13,1571
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)40.601, 120.384, 53.128
Angle α, β, γ (deg.)90.00, 106.57, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Heat shock cognate 71 kDa protein / Heat shock 70 kDa protein 8


Mass: 42086.547 Da / Num. of mol.: 1 / Fragment: UNP residues 4-381
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HSPA8, HSC70, HSP73, HSPA10 / Plasmid: pET101 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P11142
#2: Protein BAG family molecular chaperone regulator 1 / BAG-1 / Bcl-2-associated athanogene 1 / Glucocorticoid receptor-associated protein RAP46


Mass: 13157.168 Da / Num. of mol.: 1 / Fragment: UNP residues 222-334
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BAG1, HAP / Plasmid: pGEX-2T / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q99933
#3: Chemical ChemComp-TRS / 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / TRIS BUFFER


Mass: 122.143 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H12NO3 / Comment: pH buffer*YM
#4: Chemical ChemComp-3FD / 4-[[(2R,3S,4R,5R)-5-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-3,4-dihydroxy-oxolan-2-yl]methoxymethyl]benzonitrile


Mass: 556.401 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H23Cl2N7O4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 305 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.25 Å3/Da / Density % sol: 45.4 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 15% PEG3350, 0.1M Tris buffer, 25mM sodium-potassium tartrate, pH8.5, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Mar 14, 2007 / Details: mirrors
RadiationMonochromator: mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2→25 Å / Num. all: 31738 / Num. obs: 31738 / % possible obs: 96.2 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 2.62 % / Rmerge(I) obs: 0.134 / Net I/σ(I): 2.6
Reflection shellResolution: 2→2.07 Å / Redundancy: 2.63 % / Rmerge(I) obs: 0.56 / Mean I/σ(I) obs: 1.1 / % possible all: 97

-
Processing

Software
NameVersionClassification
CrystalCleardata collection
MOLREPphasing
REFMAC5.2.0019refinement
d*TREKdata reduction
d*TREKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1HX1

1hx1


Resolution: 2.2→24.92 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.924 / SU B: 13.163 / SU ML: 0.295 / Cross valid method: THROUGHOUT / σ(F): 1 / σ(I): 1 / ESU R: 0.43 / ESU R Free: 0.304 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.30384 1843 7.8 %RANDOM
Rwork0.21005 ---
obs0.21727 21904 95.77 %-
all-21904 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 48.749 Å2
Baniso -1Baniso -2Baniso -3
1--0.33 Å20 Å2-0.18 Å2
2--0.23 Å20 Å2
3---0 Å2
Refinement stepCycle: LAST / Resolution: 2.2→24.92 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3815 0 51 305 4171
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0223920
X-RAY DIFFRACTIONr_angle_refined_deg1.6361.9585288
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8775486
X-RAY DIFFRACTIONr_dihedral_angle_2_deg40.1124.917181
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.04815721
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.8741526
X-RAY DIFFRACTIONr_chiral_restr0.1040.2604
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.022911
X-RAY DIFFRACTIONr_nbd_refined0.2390.21999
X-RAY DIFFRACTIONr_nbtor_refined0.3030.22688
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1910.2323
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.220.275
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1880.223
X-RAY DIFFRACTIONr_mcbond_it0.6911.52502
X-RAY DIFFRACTIONr_mcangle_it1.20423913
X-RAY DIFFRACTIONr_scbond_it1.7931600
X-RAY DIFFRACTIONr_scangle_it2.8834.51375
LS refinement shellResolution: 2.2→2.257 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.479 146 -
Rwork0.399 1636 -
obs-1782 96.9 %

+
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