[English] 日本語
Yorodumi
- PDB-6y7t: Engineered conjugation of lysine-specific molecular tweezers with... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6y7t
TitleEngineered conjugation of lysine-specific molecular tweezers with ExoS derived peptidic inhibitor enhance affinity towards target protein 14-3-3 through ditopic binding
Components
  • 14-3-3 protein sigma
  • Exoenzyme S
KeywordsPEPTIDE BINDING PROTEIN / Protein-protein interactions / supramolecular ligands / molecular tweezers / protein recognition / hybrid ligands
Function / homology
Function and homology information


regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / keratinocyte development / keratinization / glycosyltransferase activity / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding / Activation of BAD and translocation to mitochondria ...regulation of epidermal cell division / protein kinase C inhibitor activity / positive regulation of epidermal cell differentiation / keratinocyte development / keratinization / glycosyltransferase activity / Regulation of localization of FOXO transcription factors / keratinocyte proliferation / phosphoserine residue binding / Activation of BAD and translocation to mitochondria / negative regulation of keratinocyte proliferation / establishment of skin barrier / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / protein kinase A signaling / negative regulation of stem cell proliferation / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / RHO GTPases activate PKNs / protein export from nucleus / negative regulation of innate immune response / nucleotidyltransferase activity / GTPase activator activity / protein sequestering activity / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / release of cytochrome c from mitochondria / positive regulation of protein export from nucleus / stem cell proliferation / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / negative regulation of protein kinase activity / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / intrinsic apoptotic signaling pathway in response to DNA damage / toxin activity / positive regulation of cell growth / regulation of cell cycle / cadherin binding / protein kinase binding / negative regulation of transcription by RNA polymerase II / signal transduction / extracellular space / extracellular exosome / extracellular region / identical protein binding / nucleus / cytosol / cytoplasm
Similarity search - Function
Type III secretion system effector protein YopE-like / Virulence factor YopE, GAP domain / Virulence factor YopE, GAP domain superfamily / Yersinia virulence determinant (YopE) / ADP ribosyltransferase / ADP-ribosyltransferase exoenzyme / Toxin-related mono-ADP-ribosyltransferase (TR mART) core domain profile. / 14-3-3 protein sigma / 14-3-3 proteins signature 2. / 14-3-3 protein, conserved site ...Type III secretion system effector protein YopE-like / Virulence factor YopE, GAP domain / Virulence factor YopE, GAP domain superfamily / Yersinia virulence determinant (YopE) / ADP ribosyltransferase / ADP-ribosyltransferase exoenzyme / Toxin-related mono-ADP-ribosyltransferase (TR mART) core domain profile. / 14-3-3 protein sigma / 14-3-3 proteins signature 2. / 14-3-3 protein, conserved site / 14-3-3 proteins signature 1. / 14-3-3 protein / 14-3-3 homologues / 14-3-3 domain / 14-3-3 domain superfamily / 14-3-3 protein
Similarity search - Domain/homology
ExoSTWZ molecular tweezer / 14-3-3 protein sigma / Exoenzyme S
Similarity search - Component
Biological speciesHomo sapiens (human)
Pseudomonas aeruginosa (bacteria)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsGuillory, X. / Ottmann, C.
Funding support Germany, Netherlands, 2items
OrganizationGrant numberCountry
German Research Foundation (DFG) Germany
Netherlands Organisation for Scientific Research (NWO) Netherlands
Citation
Journal: J.Am.Chem.Soc. / Year: 2021
Title: Supramolecular Enhancement of a Natural 14-3-3 Protein Ligand.
Authors: Guillory, X. / Hadrovic, I. / de Vink, P.J. / Sowislok, A. / Brunsveld, L. / Schrader, T. / Ottmann, C.
#1: Journal: J. Am. Chem. Soc. / Year: 2017
Title: The Molecular Tweezer CLR01 Stabilizes a Disordered Protein-Protein Interface.
Authors: Bier, D. / Mittal, S. / Bravo-Rodriguez, K. / Sowislok, A. / Guillory, X. / Briels, J. / Heid, C. / Bartel, M. / Wettig, B. / Brunsveld, L. / Sanchez-Garcia, E. / Schrader, T. / Ottmann, C.
#2: Journal: Nat Chem / Year: 2013
Title: Molecular tweezers modulate 14-3-3 protein-protein interactions.
Authors: Bier, D. / Rose, R. / Bravo-Rodriguez, K. / Bartel, M. / Ramirez-Anguita, J.M. / Dutt, S. / Wilch, C. / Klarner, F.G. / Sanchez-Garcia, E. / Schrader, T. / Ottmann, C.
History
DepositionMar 2, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 31, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 13, 2021Group: Data collection / Database references
Category: citation / citation_author ...citation / citation_author / database_2 / pdbx_database_proc
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _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 / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Jan 24, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 14-3-3 protein sigma
D: Exoenzyme S
E: Exoenzyme S
F: 14-3-3 protein sigma
K: 14-3-3 protein sigma
P: 14-3-3 protein sigma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)117,19515
Polymers115,1376
Non-polymers2,0599
Water6,612367
1
D: Exoenzyme S
F: 14-3-3 protein sigma
P: 14-3-3 protein sigma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)58,6098
Polymers57,5683
Non-polymers1,0415
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
A: 14-3-3 protein sigma
E: Exoenzyme S
hetero molecules

K: 14-3-3 protein sigma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)58,5867
Polymers57,5683
Non-polymers1,0184
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_555-x+1/2,y+1/2,-z+1/21
3
K: 14-3-3 protein sigma
hetero molecules

A: 14-3-3 protein sigma
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,5915
Polymers56,4532
Non-polymers1383
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation4_545-x+1/2,y-1/2,-z+1/21
Unit cell
Length a, b, c (Å)145.151, 63.119, 167.021
Angle α, β, γ (deg.)90.00, 101.29, 90.00
Int Tables number5
Space group name H-MI121

-
Components

-
Protein / Protein/peptide , 2 types, 6 molecules AFKPDE

#1: Protein
14-3-3 protein sigma / Epithelial cell marker protein 1 / Stratifin


Mass: 28226.518 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SFN, HME1 / Production host: Escherichia coli (E. coli) / References: UniProt: P31947
#2: Protein/peptide Exoenzyme S


Mass: 1115.236 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) Pseudomonas aeruginosa (bacteria) / References: UniProt: Q51451

-
Non-polymers , 4 types, 376 molecules

#3: Chemical
ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 5 / Source method: isolated from a natural source / Formula: Na
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-TWZ / ExoSTWZ molecular tweezer


Mass: 879.785 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C48H39N3O10P2 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 367 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.54 Å3/Da / Density % sol: 65.21 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7
Details: Bis-Tris Propane 0.2M sodium acetate trihydrate 20% PEG1000 10% Glycerol pH 7 Grew at 4 degree Celsius after a few days

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: EMBL/DESY, HAMBURG / Beamline: X11 / Wavelength: 0.97625 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Dec 14, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97625 Å / Relative weight: 1
ReflectionResolution: 2.5→59.9 Å / Num. obs: 51708 / % possible obs: 99.9 % / Redundancy: 6.6 % / Biso Wilson estimate: 34.12 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.129 / Rpim(I) all: 0.058 / Rrim(I) all: 0.151 / Net I/σ(I): 8.2
Reflection shellResolution: 2.5→2.57 Å / Redundancy: 6.4 % / Rmerge(I) obs: 0.803 / Mean I/σ(I) obs: 1.9 / Num. unique obs: 3691 / CC1/2: 0.796 / Rpim(I) all: 0.373 / Rrim(I) all: 0.954 / % possible all: 98.4

-
Processing

Software
NameVersionClassification
REFMAC5.8.0238refinement
DIALSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4N7G

4n7g


Resolution: 2.5→59.9 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.905 / SU B: 19.831 / SU ML: 0.229 / Cross valid method: THROUGHOUT / ESU R: 0.38 / ESU R Free: 0.275 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.26754 2689 5.2 %RANDOM
Rwork0.21895 ---
obs0.2215 49026 99.75 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 46.368 Å2
Baniso -1Baniso -2Baniso -3
1-3.93 Å2-0 Å2-0.11 Å2
2---0.4 Å2-0 Å2
3----3.23 Å2
Refinement stepCycle: 1 / Resolution: 2.5→59.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7369 0 141 367 7877
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0137720
X-RAY DIFFRACTIONr_bond_other_d0.0010.0177189
X-RAY DIFFRACTIONr_angle_refined_deg1.7021.64610429
X-RAY DIFFRACTIONr_angle_other_deg1.3171.58216696
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.185948
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.38222.707410
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.361151418
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.7541555
X-RAY DIFFRACTIONr_chiral_restr0.0760.2994
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.028627
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021558
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.9033.1773798
X-RAY DIFFRACTIONr_mcbond_other1.9023.1773797
X-RAY DIFFRACTIONr_mcangle_it2.974.7554744
X-RAY DIFFRACTIONr_mcangle_other2.9694.7564745
X-RAY DIFFRACTIONr_scbond_it2.5763.4493922
X-RAY DIFFRACTIONr_scbond_other2.5763.4483922
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other3.7615.0975686
X-RAY DIFFRACTIONr_long_range_B_refined6.23560.09931966
X-RAY DIFFRACTIONr_long_range_B_other6.22360.00731830
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.5→2.564 Å
RfactorNum. reflection% reflection
Rfree0.338 198 -
Rwork0.275 3461 -
obs--97.06 %
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)
11.15620.18280.85280.69570.25492.25930.13770.0427-0.0955-0.0067-0.0835-0.01940.2178-0.1215-0.05420.0268-0.0032-0.01110.07250.01010.08717.17350.081719.4495
24.4921-5.0059-2.20738.03870.38572.9331-0.2502-0.3205-0.35590.47640.01730.15530.050.35820.23280.1735-0.1133-0.11460.18470.13750.278824.02034.3174-18.664
31.57642.57840.49415.61972.36392.0172-0.12950.3120.0163-0.28810.2822-0.2579-0.1436-0.1213-0.15270.0491-0.0027-0.00910.19940.05790.251118.24146.202212.3908
41.6471-0.2933-1.02280.41330.02611.27710.1438-0.01430.1720.0446-0.06270.028-0.1444-0.1161-0.08110.0390.00160.05870.05950.00050.133225.925410.8091-25.4806
52.391-0.2095-0.32430.8568-0.07070.39360.108-0.10060.23830.1749-0.10440.2259-0.1084-0.1271-0.00360.0813-0.02170.0090.1203-0.01660.19895.8047-13.666550.563
62.79590.17880.66261.5716-0.09560.85790.2001-0.4153-0.34440.5219-0.1369-0.27750.24670.1268-0.06320.3366-0.0193-0.00640.14980.02350.236861.5058-7.3813-23.3276
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A-4 - 231
2X-RAY DIFFRACTION2D420 - 430
3X-RAY DIFFRACTION3E420 - 430
4X-RAY DIFFRACTION4F-4 - 231
5X-RAY DIFFRACTION5K-4 - 231
6X-RAY DIFFRACTION6P-4 - 231

+
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