[English] 日本語
Yorodumi
- PDB-6opj: Menin in complex with peptide inhibitor 25 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6opj
TitleMenin in complex with peptide inhibitor 25
Components
  • Menin
  • Peptide inhibitor 25
KeywordsPROTEIN BINDING/INHIBITOR / Protein-protein interaction inhibitor / PROTEIN BINDING-INHIBITOR complex
Function / homology
Function and homology information


negative regulation of cyclin-dependent protein serine/threonine kinase activity / Y-form DNA binding / MLL1/2 complex / osteoblast development / negative regulation of JNK cascade / T-helper 2 cell differentiation / Formation of WDR5-containing histone-modifying complexes / positive regulation of transforming growth factor beta receptor signaling pathway / negative regulation of protein phosphorylation / histone methyltransferase complex ...negative regulation of cyclin-dependent protein serine/threonine kinase activity / Y-form DNA binding / MLL1/2 complex / osteoblast development / negative regulation of JNK cascade / T-helper 2 cell differentiation / Formation of WDR5-containing histone-modifying complexes / positive regulation of transforming growth factor beta receptor signaling pathway / negative regulation of protein phosphorylation / histone methyltransferase complex / negative regulation of cell cycle / R-SMAD binding / cleavage furrow / MLL1 complex / negative regulation of osteoblast differentiation / RHO GTPases activate IQGAPs / negative regulation of DNA-binding transcription factor activity / response to UV / four-way junction DNA binding / transcription repressor complex / transcription initiation-coupled chromatin remodeling / response to gamma radiation / Post-translational protein phosphorylation / Deactivation of the beta-catenin transactivating complex / phosphoprotein binding / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / Formation of the beta-catenin:TCF transactivating complex / nuclear matrix / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / MAPK cascade / double-stranded DNA binding / protein-macromolecule adaptor activity / chromosome, telomeric region / transcription cis-regulatory region binding / endoplasmic reticulum lumen / negative regulation of cell population proliferation / DNA repair / negative regulation of DNA-templated transcription / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / chromatin / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / nucleus / cytoplasm / cytosol
Similarity search - Function
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.50065718427 Å
AuthorsLinhares, B.M. / Fortuna, P. / Cierpicki, T. / Grembecka, J. / Berlicki, L.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA200660 United States
Citation
Journal: Eur.J.Med.Chem. / Year: 2020
Title: Covalent and noncovalent constraints yield a figure eight-like conformation of a peptide inhibiting the menin-MLL interaction.
Authors: Fortuna, P. / Linhares, B.M. / Purohit, T. / Pollock, J. / Cierpicki, T. / Grembecka, J. / Berlicki, L.
#1: Journal: Acta Crystallogr D Biol Crystallogr / Year: 2010
Title: PHENIX: a comprehensive Python-based system for macromolecular structure solution.
Authors: Paul D Adams / Pavel V Afonine / Gábor Bunkóczi / Vincent B Chen / Ian W Davis / Nathaniel Echols / Jeffrey J Headd / Li-Wei Hung / Gary J Kapral / Ralf W Grosse-Kunstleve / Airlie J McCoy ...Authors: Paul D Adams / Pavel V Afonine / Gábor Bunkóczi / Vincent B Chen / Ian W Davis / Nathaniel Echols / Jeffrey J Headd / Li-Wei Hung / Gary J Kapral / Ralf W Grosse-Kunstleve / Airlie J McCoy / Nigel W Moriarty / Robert Oeffner / Randy J Read / David C Richardson / Jane S Richardson / Thomas C Terwilliger / Peter H Zwart /
Abstract: Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many ...Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics. PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms.
History
DepositionApr 25, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 2, 2020Provider: repository / Type: Initial release
Revision 1.1Sep 16, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Oct 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.3Nov 15, 2023Group: Data collection / Derived calculations / Category: chem_comp_atom / chem_comp_bond / struct_conn
Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_1 ..._chem_comp_atom.atom_id / _chem_comp_bond.atom_id_1 / _chem_comp_bond.atom_id_2 / _struct_conn.pdbx_leaving_atom_flag

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Menin
B: Peptide inhibitor 25
hetero molecules


Theoretical massNumber of molelcules
Total (without water)56,87910
Polymers56,0842
Non-polymers7958
Water12,755708
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: assay for oligomerization, FP assay
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2770 Å2
ΔGint-28 kcal/mol
Surface area19900 Å2
MethodPISA
Unit cell
Length a, b, c (Å)47.867, 78.145, 123.702
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

-
Protein / Protein/peptide , 2 types, 2 molecules AB

#1: Protein Menin


Mass: 54570.223 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) / References: UniProt: O00255*PLUS
#2: Protein/peptide Peptide inhibitor 25


Mass: 1513.787 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)

-
Non-polymers , 4 types, 716 molecules

#3: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6OS / Feature type: SUBJECT OF INVESTIGATION / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-PG4 / TETRAETHYLENE GLYCOL


Mass: 194.226 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H18O5 / Feature type: SUBJECT OF INVESTIGATION / Comment: precipitant*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 708 / 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: 2.11 Å3/Da / Density % sol: 41.81 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop
Details: 0.2 M lithium sulfate, 0.1 M HEPES, pH 7.5, 25% w/v PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.97856 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Dec 7, 2018
RadiationMonochromator: diamond(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97856 Å / Relative weight: 1
ReflectionResolution: 1.5→50 Å / Num. obs: 75018 / % possible obs: 98.9 % / Redundancy: 7.2 % / Biso Wilson estimate: 18.7727497248 Å2 / Rmerge(I) obs: 0.083 / Net I/σ(I): 18.15
Reflection shellResolution: 1.5→1.56 Å / Rmerge(I) obs: 0.574 / Num. unique obs: 7941

-
Processing

Software
NameVersionClassification
phenix.refine1.11.1_2575refinement
PHENIX1.11.1_2575refinement
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 4X5Y

4x5y


Resolution: 1.50065718427→25.975819035 Å / SU ML: 0.140044662221 / Cross valid method: FREE R-VALUE / σ(F): 1.36249709392 / Phase error: 19.2767683358
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.197431374728 3621 4.88532110092 %
Rwork0.168395264883 70499 -
obs0.169817677969 74120 98.8293021147 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 25.3451975915 Å2
Refinement stepCycle: LAST / Resolution: 1.50065718427→25.975819035 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3714 0 44 708 4466
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.005046527966453891
X-RAY DIFFRACTIONf_angle_d0.9095309740285273
X-RAY DIFFRACTIONf_chiral_restr0.0501727198402587
X-RAY DIFFRACTIONf_plane_restr0.00393863039603666
X-RAY DIFFRACTIONf_dihedral_angle_d14.50977081572308
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.5007-1.52040.2878314657841270.245376196672522X-RAY DIFFRACTION93.7035726919
1.5204-1.54120.2597512874881320.2354424451212747X-RAY DIFFRACTION100
1.5412-1.56320.2371308705191440.2265439735652672X-RAY DIFFRACTION100
1.5632-1.58660.239912229981350.2106101280192736X-RAY DIFFRACTION100
1.5866-1.61140.2074841380471440.2045424048812679X-RAY DIFFRACTION100
1.6114-1.63780.2643944268161500.2000614655292746X-RAY DIFFRACTION100
1.6378-1.6660.2344747928641190.1938715732512712X-RAY DIFFRACTION100
1.666-1.69630.2193711164291330.1926671200882718X-RAY DIFFRACTION100
1.6963-1.72890.2092507236821340.1995897910922703X-RAY DIFFRACTION100
1.7289-1.76420.2047641176591200.1887133364452745X-RAY DIFFRACTION100
1.7642-1.80260.2299870916951390.1860659230252702X-RAY DIFFRACTION99.9648135116
1.8026-1.84450.2423587647871410.1794302303212743X-RAY DIFFRACTION99.9653379549
1.8445-1.89060.2209575614781300.1854769917352679X-RAY DIFFRACTION99.9644128114
1.8906-1.94170.2074817132511400.1743765145222737X-RAY DIFFRACTION99.8611593197
1.9417-1.99880.2012303842081680.1739403859552751X-RAY DIFFRACTION99.829001368
1.9988-2.06330.2012245118951490.1685892364592690X-RAY DIFFRACTION99.6140350877
2.0633-2.1370.1944777480031420.1555812698392738X-RAY DIFFRACTION99.6195088205
2.137-2.22250.1790958973851510.1557896402132656X-RAY DIFFRACTION99.2223400495
2.2225-2.32360.2082397051581340.1552266779392754X-RAY DIFFRACTION99.2098935074
2.3236-2.4460.2280826383821520.156081963062720X-RAY DIFFRACTION99.1712707182
2.446-2.59920.1656599523631480.1647669770942721X-RAY DIFFRACTION98.8628532047
2.5992-2.79960.2139547468931420.162148488782741X-RAY DIFFRACTION98.766700925
2.7996-3.0810.1969037451321490.1647947021392734X-RAY DIFFRACTION98.9022298456
3.081-3.52580.1432855964211380.1526327735872731X-RAY DIFFRACTION97.4855589534
3.5258-4.43860.1990490857021240.1446705204922633X-RAY DIFFRACTION92.5478348439
4.4386-25.97970.1845929037141360.1793619541312789X-RAY DIFFRACTION93.6299615877

+
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