[English] 日本語
Yorodumi
- PDB-7acd: Crystal structure of the human METTL3-METTL14 complex with compou... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7acd
TitleCrystal structure of the human METTL3-METTL14 complex with compound T30 (UZH1a)
Components(N6-adenosine-methyltransferase ...) x 2
KeywordsTRANSFERASE / Inhibitor / Complex / METTL3 / Sinefungin / METTL14
Function / homology
Function and homology information


negative regulation of hematopoietic progenitor cell differentiation / positive regulation of cap-independent translational initiation / mRNA m6A methyltransferase / mRNA m(6)A methyltransferase activity / RNA N6-methyladenosine methyltransferase complex / RNA methylation / endothelial to hematopoietic transition / regulation of meiotic cell cycle / RNA methyltransferase activity / primary miRNA processing ...negative regulation of hematopoietic progenitor cell differentiation / positive regulation of cap-independent translational initiation / mRNA m6A methyltransferase / mRNA m(6)A methyltransferase activity / RNA N6-methyladenosine methyltransferase complex / RNA methylation / endothelial to hematopoietic transition / regulation of meiotic cell cycle / RNA methyltransferase activity / primary miRNA processing / forebrain radial glial cell differentiation / dosage compensation by inactivation of X chromosome / oxidoreductase complex / S-adenosyl-L-methionine binding / gliogenesis / mRNA stabilization / regulation of hematopoietic stem cell differentiation / mRNA modification / regulation of neuron differentiation / regulation of T cell differentiation / negative regulation of type I interferon-mediated signaling pathway / oogenesis / stem cell population maintenance / mRNA destabilization / Processing of Capped Intron-Containing Pre-mRNA / negative regulation of Notch signaling pathway / positive regulation of translation / response to nutrient levels / circadian rhythm / mRNA splicing, via spliceosome / mRNA processing / cellular response to UV / spermatogenesis / nuclear speck / nuclear body / protein heterodimerization activity / innate immune response / mRNA binding / DNA damage response / Golgi apparatus / nucleoplasm / nucleus / cytosol
Similarity search - Function
N6-adenosine-methyltransferase non-catalytic subunit METTL14-like / mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase-like (MT-A70-like) family profile. / N6-adenosine-methyltransferase MT-A70-like / mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase (EC 2.1.1.62) family profile. / MT-A70-like / MT-A70 / MT-A70-like family profile. / S-adenosyl-L-methionine-dependent methyltransferase superfamily
Similarity search - Domain/homology
ACETATE ION / Chem-R72 / N(6)-adenosine-methyltransferase catalytic subunit METTL3 / N(6)-adenosine-methyltransferase non-catalytic subunit METTL14
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsBedi, R.K. / Huang, D. / Caflisch, A.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Swiss National Science Foundation310030B_189363 Switzerland
Citation
Journal: Chemmedchem / Year: 2021
Title: METTL3 Inhibitors for Epitranscriptomic Modulation of Cellular Processes.
Authors: Moroz-Omori, E.V. / Huang, D. / Kumar Bedi, R. / Cheriyamkunnel, S.J. / Bochenkova, E. / Dolbois, A. / Rzeczkowski, M.D. / Li, Y. / Wiedmer, L. / Caflisch, A.
#1: Journal: Biorxiv / Year: 2020
Title: METTL3 inhibitors for epitranscriptomic modulation of cellular processes
Authors: Moroz-Omori, E.V. / Huang, D. / Bedi, R.K. / Cheriyamkunnel, S.J. / Bochenkova, E. / Dolbois, A. / Rzeczkowski, M.D. / Wiedmer, L. / Caflisch, A.
#2: Journal: J Chem Inf Model / Year: 2020
Title: Structural and Dynamic Insights into Redundant Function of YTHDF Proteins.
Authors: Li, Y. / Bedi, R.K. / Moroz-Omori, E.V. / Caflisch, A.
History
DepositionSep 10, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 28, 2020Provider: repository / Type: Initial release
Revision 1.1Nov 4, 2020Group: Database references / Category: citation / citation_author / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Nov 11, 2020Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _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
Revision 2.0Mar 24, 2021Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations / Refinement description / Structure summary
Category: atom_site / citation ...atom_site / citation / entity / pdbx_distant_solvent_atoms / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly / pdbx_struct_sheet_hbond / pdbx_struct_special_symmetry / pdbx_validate_close_contact / pdbx_validate_peptide_omega / pdbx_validate_rmsd_angle / pdbx_validate_symm_contact / pdbx_validate_torsion / refine / refine_hist / refine_ls_restr / refine_ls_shell / software / struct_conn / struct_conn_type / struct_mon_prot_cis
Item: _citation.journal_abbrev / _entity.formula_weight ..._citation.journal_abbrev / _entity.formula_weight / _entity.pdbx_description / _entity.pdbx_number_of_molecules / _pdbx_distant_solvent_atoms.auth_seq_id / _pdbx_distant_solvent_atoms.neighbor_macromolecule_distance / _pdbx_entity_nonpoly.comp_id / _pdbx_entity_nonpoly.name / _pdbx_struct_assembly.details / _pdbx_struct_assembly.method_details / _pdbx_struct_sheet_hbond.range_1_auth_comp_id / _pdbx_struct_sheet_hbond.range_1_auth_seq_id / _pdbx_struct_sheet_hbond.range_1_label_comp_id / _pdbx_struct_sheet_hbond.range_1_label_seq_id / _pdbx_struct_special_symmetry.auth_seq_id / _pdbx_validate_close_contact.auth_asym_id_1 / _pdbx_validate_close_contact.auth_asym_id_2 / _pdbx_validate_close_contact.auth_comp_id_1 / _pdbx_validate_close_contact.auth_seq_id_1 / _pdbx_validate_close_contact.auth_seq_id_2 / _pdbx_validate_close_contact.dist / _pdbx_validate_peptide_omega.omega / _refine.B_iso_mean / _refine.ls_R_factor_R_free / _refine.ls_R_factor_R_work / _refine.ls_R_factor_obs / _refine.overall_SU_ML / _refine.pdbx_overall_phase_error / _refine_hist.number_atoms_solvent / _refine_hist.number_atoms_total / _refine_ls_restr.dev_ideal / _refine_ls_shell.R_factor_R_free / _refine_ls_shell.R_factor_R_work / _refine_ls_shell.percent_reflns_obs / _software.version / _struct_mon_prot_cis.pdbx_omega_angle
Description: Ligand geometry / Details: Minor correction based on latest MD simulation / Provider: author / Type: Coordinate replacement
Revision 2.1Jul 21, 2021Group: Database references / Category: citation / citation_author
Revision 2.2Oct 13, 2021Group: Data collection / Database references
Category: citation / citation_author ...citation / citation_author / database_2 / pdbx_database_proc
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.identifier_ORCID / _citation_author.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 2.3Jan 31, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / pdbx_initial_refinement_model
Item: _citation.journal_id_ISSN
Revision 2.4Nov 13, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: N6-adenosine-methyltransferase catalytic subunit
B: N6-adenosine-methyltransferase non-catalytic subunit
hetero molecules


Theoretical massNumber of molelcules
Total (without water)62,4075
Polymers61,7652
Non-polymers6423
Water2,216123
1
A: N6-adenosine-methyltransferase catalytic subunit
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,7032
Polymers28,1441
Non-polymers5591
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: N6-adenosine-methyltransferase non-catalytic subunit
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7053
Polymers33,6211
Non-polymers832
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)63.800, 63.800, 224.920
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number154
Space group name H-MP3221
Space group name HallP322"
Symmetry operation#1: x,y,z
#2: -y,x-y,z+2/3
#3: -x+y,-x,z+1/3
#4: x-y,-y,-z+1/3
#5: -x,-x+y,-z+2/3
#6: y,x,-z
Components on special symmetry positions
IDModelComponents
11A-744-

HOH

21B-579-

HOH

-
Components

-
N6-adenosine-methyltransferase ... , 2 types, 2 molecules AB

#1: Protein N6-adenosine-methyltransferase catalytic subunit / Methyltransferase-like protein 3 / hMETTL3 / N6-adenosine-methyltransferase 70 kDa subunit / MT-A70


Mass: 28144.080 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: METTL3, MTA70 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q86U44, mRNA m6A methyltransferase
#2: Protein N6-adenosine-methyltransferase non-catalytic subunit / Methyltransferase-like protein 14 / hMETTL14


Mass: 33621.246 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: METTL14, KIAA1627 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9HCE5

-
Non-polymers , 4 types, 126 molecules

#3: Chemical ChemComp-R72 / 4-[(4,4-dimethylpiperidin-1-yl)methyl]-2-oxidanyl-~{N}-[[(3~{R})-3-oxidanyl-1-[6-[(phenylmethyl)amino]pyrimidin-4-yl]piperidin-3-yl]methyl]benzamide


Mass: 558.714 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C32H42N6O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#5: Chemical ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H3O2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 123 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.14 Å3/Da / Density % sol: 42.51 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / Details: 20% PEG 3350, 400mM Mg acetate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: Feb 16, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5→44.98 Å / Num. obs: 19248 / % possible obs: 99.9 % / Redundancy: 9.72 % / Biso Wilson estimate: 44.05 Å2 / CC1/2: 0.996 / Net I/σ(I): 11.33
Reflection shellResolution: 2.5→2.65 Å / Num. unique obs: 3051 / CC1/2: 0.609

-
Processing

Software
NameVersionClassification
XDSdata reduction
XSCALEdata scaling
PHASERphasing
PHENIX1.19.1_4122refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5L6D

5l6d


Resolution: 2.5→44.48 Å / SU ML: 0.312 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 23.9113
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2317 959 5 %
Rwork0.1874 18203 -
obs0.1896 19162 99.81 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 44.88 Å2
Refinement stepCycle: LAST / Resolution: 2.5→44.48 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3439 0 46 123 3608
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00863594
X-RAY DIFFRACTIONf_angle_d1.06534897
X-RAY DIFFRACTIONf_chiral_restr0.0557531
X-RAY DIFFRACTIONf_plane_restr0.0082632
X-RAY DIFFRACTIONf_dihedral_angle_d16.0448488
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.5-2.630.31351340.23822551X-RAY DIFFRACTION99.52
2.63-2.80.33591330.24542522X-RAY DIFFRACTION99.81
2.8-3.020.31951350.24262559X-RAY DIFFRACTION99.67
3.02-3.320.25851350.20312571X-RAY DIFFRACTION99.93
3.32-3.80.2441370.17312594X-RAY DIFFRACTION99.96
3.8-4.780.16591380.14572620X-RAY DIFFRACTION99.96
4.79-44.480.20351470.18592786X-RAY DIFFRACTION99.83

+
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