[English] 日本語
Yorodumi
- PDB-5ddf: Menin in complex with MI-273 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ddf
TitleMenin in complex with MI-273
ComponentsMenin
KeywordsPROTEIN BINDING/INHIBITOR / PROTEIN BINDING / 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 / histone methyltransferase complex / negative regulation of protein phosphorylation ...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 / histone methyltransferase complex / negative regulation of protein phosphorylation / R-SMAD binding / negative regulation of cell cycle / cleavage furrow / MLL1 complex / negative regulation of osteoblast differentiation / RHO GTPases activate IQGAPs / response to UV / four-way junction DNA binding / transcription repressor complex / negative regulation of DNA-binding transcription factor activity / transcription initiation-coupled chromatin remodeling / response to gamma radiation / phosphoprotein binding / Post-translational protein phosphorylation / Deactivation of the beta-catenin transactivating complex / 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 / cytosol / cytoplasm
Similarity search - Function
Chem-5A1 / DI(HYDROXYETHYL)ETHER / Menin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.66 Å
AuthorsPollock, J. / Dmitry, B. / Cierpicki, T. / Grembecka, J.
Funding support United States, 8items
OrganizationGrant numberCountry
American Cancer SocietyRSG-11-082-01-DMC United States
American Cancer SocietyRSG-13-130-01-CDD United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA181185 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R01 CA160467 United States
Leukemia & Lymphoma Society6116-12 United States
Leukemia & Lymphoma Society1215-14 United States
Department of Energy (DOE, United States)DE-AC02-06CH11357 United States
LS-CAT Sector 21085P1000817 United States
CitationJournal: J.Med.Chem. / Year: 2015
Title: Rational Design of Orthogonal Multipolar Interactions with Fluorine in Protein-Ligand Complexes.
Authors: Pollock, J. / Borkin, D. / Lund, G. / Purohit, T. / Dyguda-Kazimierowicz, E. / Grembecka, J. / Cierpicki, T.
History
DepositionAug 24, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 9, 2015Provider: repository / Type: Initial release
Revision 1.1Oct 14, 2015Group: Database references
Revision 1.2Sep 27, 2017Group: Author supporting evidence / Database references / Derived calculations
Category: citation / pdbx_audit_support / pdbx_struct_oper_list
Item: _citation.journal_id_CSD / _pdbx_audit_support.funding_organization / _pdbx_struct_oper_list.symmetry_operation
Revision 1.3Dec 4, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Sep 27, 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Menin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,92311
Polymers54,5701
Non-polymers1,35310
Water8,197455
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)48.553, 80.189, 124.989
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Menin


Mass: 54570.223 Da / Num. of mol.: 1 / Fragment: UNP residues 1-459, 537-593 / Mutation: A541T
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MEN1, SCG2 / Production host: Escherichia coli (E. coli) / References: UniProt: O00255

-
Non-polymers , 6 types, 465 molecules

#2: Chemical ChemComp-5A1 / 4-[4-(5,5-dimethyl-4,5-dihydro-1,3-thiazol-2-yl)piperazin-1-yl]-6-(pentafluoroethyl)thieno[2,3-d]pyrimidine / MI-273


Mass: 451.480 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H18F5N5S2
#3: Chemical
ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-PG4 / TETRAETHYLENE GLYCOL


Mass: 194.226 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H18O5 / Comment: precipitant*YM
#5: Chemical ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O3
#6: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 455 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.23 Å3/Da / Density % sol: 44.85 %
Crystal growTemperature: 283 K / Method: vapor diffusion, sitting drop / pH: 8
Details: 0.2 M ammonium acetate, 0.1 M HEPES and 25% w/v PEG 3,350. This solution was mixed 1:1 with 2.5mg/mL protein in 50mM Tris-HCl, 50mM NaCl, and 1mM TCEP. Prior to data collection, crystals ...Details: 0.2 M ammonium acetate, 0.1 M HEPES and 25% w/v PEG 3,350. This solution was mixed 1:1 with 2.5mg/mL protein in 50mM Tris-HCl, 50mM NaCl, and 1mM TCEP. Prior to data collection, crystals were transferred into a cryo-solution containing 20% PEG550 MME and flash-frozen in liquid nitrogen

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 0.97928 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Aug 11, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97928 Å / Relative weight: 1
ReflectionResolution: 1.66→50 Å / Num. obs: 58205 / % possible obs: 99.5 % / Redundancy: 5.9 % / Rmerge(I) obs: 0.116 / Χ2: 1.501 / Net I/av σ(I): 18.943 / Net I/σ(I): 7.2 / Num. measured all: 342112
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2% possible all
1.66-1.695.40.78328060.66997.2
1.69-1.725.50.65328280.64998.1
1.72-1.755.40.6128370.9398.3
1.75-1.795.50.51128380.65399
1.79-1.835.50.45428800.68899.1
1.83-1.875.60.38628460.71199.1
1.87-1.925.60.35728780.81299.7
1.92-1.975.60.28629010.97599.7
1.97-2.035.70.23429030.999.9
2.03-2.095.80.2082864199.9
2.09-2.175.90.17229231.09999.9
2.17-2.255.90.16128881.236100
2.25-2.3660.13429231.35100
2.36-2.486.10.13129231.598100
2.48-2.636.20.12129211.803100
2.63-2.846.30.10429451.997100
2.84-3.126.40.09129532.365100
3.12-3.586.50.07729602.946100
3.58-4.56.40.06630263.395100
4.5-5060.05831622.80499.7

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
REFMAC5.7.0032refinement
PDB_EXTRACT3.15data extraction
HKL-2000data reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4GPQ

4gpq


Resolution: 1.66→49.34 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.954 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.089 / ESU R Free: 0.088 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.1884 2934 5.1 %RANDOM
Rwork0.1575 ---
obs0.1591 55111 99.18 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 181.6 Å2 / Biso mean: 19.443 Å2 / Biso min: 5.34 Å2
Baniso -1Baniso -2Baniso -3
1-0.85 Å20 Å2-0 Å2
2---0.04 Å2-0 Å2
3----0.8 Å2
Refinement stepCycle: final / Resolution: 1.66→49.34 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3618 0 80 455 4153
Biso mean--39.69 31.47 -
Num. residues----465
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0170.023842
X-RAY DIFFRACTIONr_bond_other_d00.023620
X-RAY DIFFRACTIONr_angle_refined_deg1.8281.9765230
X-RAY DIFFRACTIONr_angle_other_deg3.6473.0048303
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4955481
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.73823.953172
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.68115618
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.8851523
X-RAY DIFFRACTIONr_chiral_restr0.1190.2587
X-RAY DIFFRACTIONr_gen_planes_refined0.010.024344
X-RAY DIFFRACTIONr_gen_planes_other0.020.02888
X-RAY DIFFRACTIONr_mcbond_it4.3395.451884
X-RAY DIFFRACTIONr_mcbond_other4.3385.4561885
X-RAY DIFFRACTIONr_mcangle_it5.3928.5112358
LS refinement shellResolution: 1.66→1.703 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.274 196 -
Rwork0.206 3802 -
all-3998 -
obs--93.45 %

+
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