[English] 日本語
Yorodumi
- PDB-5aqt: Fragment-based screening of HSP70 sheds light on the functional r... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5aqt
TitleFragment-based screening of HSP70 sheds light on the functional role of ATP-binding site residues
Components
  • BAG FAMILY MOLECULAR CHAPERONE REGULATOR 1
  • HEAT SHOCK COGNATE 71 KDA PROTEIN
KeywordsCHAPERONE / HEAT SHOCK PROTEIN / HSP70 / HSP72 / HSC70 / ATPASE / BAG1 / FRAGMENT
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 / clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane / Lipophagy / Respiratory syncytial virus genome transcription / GABA synthesis, release, reuptake and degradation / protein targeting to lysosome involved in chaperone-mediated autophagy / protein carrier chaperone ...lumenal side of lysosomal membrane / regulation of protein import / negative regulation of supramolecular fiber organization / chaperone-mediated autophagy translocation complex disassembly / clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane / Lipophagy / Respiratory syncytial virus genome transcription / GABA synthesis, release, reuptake and degradation / protein targeting to lysosome involved in chaperone-mediated autophagy / protein carrier chaperone / adenyl-nucleotide exchange factor activity / positive regulation of smooth muscle cell apoptotic process / clathrin coat disassembly / C3HC4-type RING finger domain binding / CHL1 interactions / negative regulation of NLRP3 inflammasome complex assembly / regulation of protein complex stability / ATP-dependent protein disaggregase activity / membrane organization / 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 / : / Prp19 complex / Regulation of HSF1-mediated heat shock response / HSF1-dependent transactivation / response to unfolded protein / regulation of protein-containing complex assembly / Attenuation phase / ATP metabolic process / Protein methylation / heat shock protein binding / protein folding chaperone / mRNA Splicing - Major Pathway / lysosomal lumen / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / cellular response to starvation / AUF1 (hnRNP D0) binds and destabilizes mRNA / spliceosomal complex / ATP-dependent protein folding chaperone / G protein-coupled receptor binding / Late endosomal microautophagy / mRNA splicing, via spliceosome / PKR-mediated signaling / regulation of protein stability / 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 / apoptotic process / ubiquitin protein ligase binding / Neutrophil degranulation / 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 / Nucleotidyltransferase; domain 5 / Ubiquitin homologues / 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-5P7 / Heat shock cognate 71 kDa protein / BAG family molecular chaperone regulator 1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsJones, A.M. / Westwood, I.M. / Osborne, J.D. / Matthews, T.P. / Cheeseman, M.D. / Rowlands, M.G. / Jeganathan, F. / Burke, R. / Lee, D. / Kadi, N. ...Jones, A.M. / Westwood, I.M. / Osborne, J.D. / Matthews, T.P. / Cheeseman, M.D. / Rowlands, M.G. / Jeganathan, F. / Burke, R. / Lee, D. / Kadi, N. / Liu, M. / Richards, M. / McAndrew, C. / Yahya, N. / Dobson, S.E. / Jones, K. / Workman, P. / Collins, I. / van Montfort, R.L.M.
CitationJournal: Sci Rep / Year: 2016
Title: A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms.
Authors: Jones, A.M. / Westwood, I.M. / Osborne, J.D. / Matthews, T.P. / Cheeseman, M.D. / Rowlands, M.G. / Jeganathan, F. / Burke, R. / Lee, D. / Kadi, N. / Liu, M. / Richards, M. / McAndrew, C. / ...Authors: Jones, A.M. / Westwood, I.M. / Osborne, J.D. / Matthews, T.P. / Cheeseman, M.D. / Rowlands, M.G. / Jeganathan, F. / Burke, R. / Lee, D. / Kadi, N. / Liu, M. / Richards, M. / McAndrew, C. / Yahya, N. / Dobson, S.E. / Jones, K. / Workman, P. / Collins, I. / van Montfort, R.L.
History
DepositionSep 22, 2015Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 5, 2016Provider: repository / Type: Initial release
Revision 1.1Sep 13, 2017Group: Data collection / Database references / Category: citation / citation_author / diffrn_detector
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.name / _diffrn_detector.type
Revision 1.2Jan 10, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3Nov 6, 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)57,02512
Polymers55,9192
Non-polymers1,10610
Water3,783210
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4180 Å2
ΔGint3.8 kcal/mol
Surface area22190 Å2
MethodPISA
Unit cell
Length a, b, c (Å)115.237, 40.840, 131.959
Angle α, β, γ (deg.)90.00, 117.99, 90.00
Int Tables number5
Space group name H-MC121

-
Components

-
Protein , 2 types, 2 molecules AB

#1: Protein HEAT SHOCK COGNATE 71 KDA PROTEIN / HEAT SHOCK 70 KDA PROTEIN 8 / LIPOPOLYSACCHARIDE-ASSOCIATED PROTEIN 1 / LAP-1 / LPS-ASSOCIATED ...HEAT SHOCK 70 KDA PROTEIN 8 / LIPOPOLYSACCHARIDE-ASSOCIATED PROTEIN 1 / LAP-1 / LPS-ASSOCIATED PROTEIN 1 / HEAT SHOCK 70 KDA PROT EIN 8 / LIPOPOLYSACCHARIDE-ASSOCIATED PROTEIN 1 / LAP-1 / LPS-ASSOCIA TED PROTEIN 1


Mass: 42406.980 Da / Num. of mol.: 1 / Fragment: NUCLEOTIDE BINDING DOMAIN, UNP RESIDUES 1-381
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PGEX-6P-1 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 / Variant (production host): AI / References: UniProt: P11142, EC: 3.6.3.51
#2: Protein BAG FAMILY MOLECULAR CHAPERONE REGULATOR 1 / BAG-1 / BCL-2-ASSOCIATED ATHANOGENE 1


Mass: 13511.571 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 222-334
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PGEX-6P-1 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21 / Variant (production host): AI / References: UniProt: Q99933

-
Non-polymers , 5 types, 220 molecules

#3: Chemical ChemComp-5P7 / (1S,2R,3R,5R)-3-(hydroxymethyl)-5-(quinazolin-4-ylamino)cyclopentane-1,2-diol


Mass: 275.303 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H17N3O3
#4: 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
#5: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#6: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C3H8O3
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 210 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.45 Å3/Da / Density % sol: 49.83 % / Description: NONE
Crystal growpH: 8.5
Details: 16-26% (W/V) PEG3350, 0.1 M K-NA TARTRATE, 0.1 M TRIS.HCL PH 8.5 AND 25% (V/V) GLYCEROL

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.92
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Sep 29, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.92 Å / Relative weight: 1
ReflectionResolution: 1.9→58.26 Å / Num. obs: 36309 / % possible obs: 83.9 % / Observed criterion σ(I): 0 / Redundancy: 3 % / Biso Wilson estimate: 28.21 Å2 / Rmerge(I) obs: 0.06 / Net I/σ(I): 9.3
Reflection shellResolution: 1.9→1.94 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.61 / Mean I/σ(I) obs: 1.7 / % possible all: 70.6

-
Processing

Software
NameVersionClassification
BUSTER2.10.2refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1HX1

1hx1


Resolution: 1.9→58.26 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.917 / SU R Cruickshank DPI: 0.163 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.164 / SU Rfree Blow DPI: 0.149 / SU Rfree Cruickshank DPI: 0.149
RfactorNum. reflection% reflectionSelection details
Rfree0.2224 1784 4.92 %RANDOM
Rwork0.1803 ---
obs0.1823 36291 83.73 %-
Displacement parametersBiso mean: 40.54 Å2
Baniso -1Baniso -2Baniso -3
1--3.7928 Å20 Å2-1.7948 Å2
2--3.4867 Å20 Å2
3---0.3061 Å2
Refine analyzeLuzzati coordinate error obs: 0.236 Å
Refinement stepCycle: LAST / Resolution: 1.9→58.26 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3755 0 72 210 4037
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.013887HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.045254HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1364SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes108HARMONIC2
X-RAY DIFFRACTIONt_gen_planes576HARMONIC5
X-RAY DIFFRACTIONt_it3887HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.73
X-RAY DIFFRACTIONt_other_torsion16.52
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion526SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies1HARMONIC1
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact4572SEMIHARMONIC4
LS refinement shellResolution: 1.9→1.96 Å / Total num. of bins used: 18
RfactorNum. reflection% reflection
Rfree0.2413 108 4.31 %
Rwork0.2575 2400 -
all0.2569 2508 -
obs--70.6 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.4161-0.00160.61623.0516-0.4922.22960.14240.08420.1005-0.1382-0.2872-0.22170.0620.24630.14480.08030.1622-0.07-0.08320.0186-0.191973.94680.0068138.3834
20.9820.10930.65791.3516-0.19343.5977-0.00650.28440.0701-0.3603-0.0762-0.083-0.05490.08860.08270.11980.1626-0.0478-0.05120.0179-0.182567.9234-2.0077127.3182
30.9129-0.56010.82323.30060.89576.78790.09970.4954-0.0394-0.2757-0.0390.2458-0.2312-0.3351-0.06070.02630.1653-0.12660.10140.0128-0.169649.94365.504130.893
40.6799-0.3628-0.78431.74871.05451.770.10050.0214-0.0011-0.243-0.16890.3451-0.13150.06880.0683-0.00310.0441-0.0527-0.0737-0.0110.005658.60073.1671164.1274
51.3588-0.72070.16651.198-0.57622.93820.17340.153-0.072-0.182-0.12050.1368-0.2916-0.532-0.0529-0.0250.1411-0.0939-0.0573-0.0213-0.11454.32171.3137154.5465
62.5972-0.92870.21370.7102-1.41683.795-0.0039-0.1479-0.0843-0.25290.15460.32670.148-0.5313-0.15070.02180.1116-0.17110.0681-0.0343-0.113948.3666-2.3331136.2295
7-0.1383-0.68690.09330-0.00320.1383-0.0172-0.09430.05560.0320.00140.0715-0.0236-0.05450.01580.00630.0664-0.0322-0.0677-0.02940.076153.9565-29.6255175.4842
85.98162.2456-1.38341.1923-0.89210.8264-0.01910.0867-0.1348-0.0228-0.0352-0.04710.14440.13210.0543-0.01710.0626-0.0349-0.0395-0.03570.030781.42-18.7593162.8913
94.65480.7433-1.48392.2185-0.43131.07470.04790.07680.0402-0.0995-0.0556-0.06080.02320.09340.0078-0.02260.0372-0.0651-0.01270.0055-0.079977.7549-10.5499160.5866
103.13371.0692-0.56611.68460.16761.6450.0859-0.1026-0.02030.0335-0.0983-0.1025-0.04420.31020.01240.03010.0439-0.0595-0.02150.0251-0.019876.4709-12.0465169.1327
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{A|1 - 115}
2X-RAY DIFFRACTION2{A|116 - 182}
3X-RAY DIFFRACTION3{A|183 - 229}
4X-RAY DIFFRACTION4{A|230 - 249}
5X-RAY DIFFRACTION5{A|250 - 343}
6X-RAY DIFFRACTION6{A|344 - 381}
7X-RAY DIFFRACTION7{B|146 - 152}
8X-RAY DIFFRACTION8{B|153 - 192}
9X-RAY DIFFRACTION9{B|193 - 230}
10X-RAY DIFFRACTION10{B|231 - 260}

+
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