[English] 日本語
Yorodumi
- PDB-6mbo: GLP Methyltransferase with Inhibitor EML741-P212121 Crystal Form -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6mbo
TitleGLP Methyltransferase with Inhibitor EML741-P212121 Crystal Form
ComponentsHistone-lysine N-methyltransferase EHMT1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / Histone / H3 / Methylation Inhibition / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


[histone H3]-lysine9 N-methyltransferase / peptidyl-lysine monomethylation / peptidyl-lysine dimethylation / histone H3K27 methyltransferase activity / histone H3K9 methyltransferase activity / histone H3K9me2 methyltransferase activity / protein-lysine N-methyltransferase activity / C2H2 zinc finger domain binding / DNA methylation-dependent constitutive heterochromatin formation / Transcriptional Regulation by E2F6 ...[histone H3]-lysine9 N-methyltransferase / peptidyl-lysine monomethylation / peptidyl-lysine dimethylation / histone H3K27 methyltransferase activity / histone H3K9 methyltransferase activity / histone H3K9me2 methyltransferase activity / protein-lysine N-methyltransferase activity / C2H2 zinc finger domain binding / DNA methylation-dependent constitutive heterochromatin formation / Transcriptional Regulation by E2F6 / regulation of embryonic development / Transcriptional Regulation by VENTX / response to fungicide / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / transcription corepressor binding / Transferases; Transferring one-carbon groups; Methyltransferases / methyltransferase activity / Regulation of TP53 Activity through Methylation / PKMTs methylate histone lysines / p53 binding / chromatin organization / positive regulation of cold-induced thermogenesis / Senescence-Associated Secretory Phenotype (SASP) / nuclear body / negative regulation of DNA-templated transcription / chromatin / negative regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm / nucleus
Similarity search - Function
Histone-lysine N-methyltransferase EHMT1 / Histone-lysine N-methyltransferase EHMT1/EHMT2 / : / Histone-lysine N-methyltransferase EHMT1/EHMT2, Cys-rich region / Pre-SET motif / Pre-SET domain / Pre-SET domain profile. / N-terminal to some SET domains / Beta-clip-like / SET domain ...Histone-lysine N-methyltransferase EHMT1 / Histone-lysine N-methyltransferase EHMT1/EHMT2 / : / Histone-lysine N-methyltransferase EHMT1/EHMT2, Cys-rich region / Pre-SET motif / Pre-SET domain / Pre-SET domain profile. / N-terminal to some SET domains / Beta-clip-like / SET domain / Ankyrin repeats (many copies) / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain / SET domain superfamily / SET domain profile. / SET domain / Beta Complex / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / Mainly Beta
Similarity search - Domain/homology
Chem-JDG / S-ADENOSYL-L-HOMOCYSTEINE / Histone-lysine N-methyltransferase EHMT1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.591 Å
AuthorsHorton, J.R. / Cheng, X.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM049245-23 United States
CitationJournal: J. Med. Chem. / Year: 2019
Title: Discovery of a Novel Chemotype of Histone Lysine Methyltransferase EHMT1/2 (GLP/G9a) Inhibitors: Rational Design, Synthesis, Biological Evaluation, and Co-crystal Structure.
Authors: Milite, C. / Feoli, A. / Horton, J.R. / Rescigno, D. / Cipriano, A. / Pisapia, V. / Viviano, M. / Pepe, G. / Amendola, G. / Novellino, E. / Cosconati, S. / Cheng, X. / Castellano, S. / Sbardella, G.
History
DepositionAug 30, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 27, 2019Provider: repository / Type: Initial release
Revision 1.1Mar 27, 2019Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title
Revision 1.2Jan 1, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Oct 11, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone-lysine N-methyltransferase EHMT1
B: Histone-lysine N-methyltransferase EHMT1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,72130
Polymers60,4652
Non-polymers4,25628
Water10,629590
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5250 Å2
ΔGint-25 kcal/mol
Surface area24560 Å2
Unit cell
Length a, b, c (Å)87.732, 88.306, 95.124
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 2 molecules AB

#1: Protein Histone-lysine N-methyltransferase EHMT1 / Euchromatic histone-lysine N-methyltransferase 1 / Eu-HMTase1 / G9a-like protein 1 / GLP1 / Histone ...Euchromatic histone-lysine N-methyltransferase 1 / Eu-HMTase1 / G9a-like protein 1 / GLP1 / Histone H3-K9 methyltransferase 5 / H3-K9-HMTase 5 / Lysine N-methyltransferase 1D


Mass: 30232.373 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EHMT1, EUHMTASE1, GLP, KIAA1876, KMT1D / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3)
References: UniProt: Q9H9B1, histone-lysine N-methyltransferase

-
Non-polymers , 5 types, 618 molecules

#2: Chemical
ChemComp-JDG / 2-cyclohexyl-7-methoxy-N-[1-(propan-2-yl)piperidin-4-yl]-8-[3-(pyrrolidin-1-yl)propoxy]-3H-1,4-benzodiazepin-5-amine


Mass: 523.753 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C31H49N5O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Zn
#4: Chemical ChemComp-SAH / S-ADENOSYL-L-HOMOCYSTEINE


Type: L-peptide linking / Mass: 384.411 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H20N6O5S
#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 14 / Source method: obtained synthetically / Formula: C2H6O2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 590 / 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: 3.05 Å3/Da / Density % sol: 59.63 %
Crystal growTemperature: 292 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: 15% PEG 4000, 20% isopropanol and 100mM citrate (pH 5.5)

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Apr 23, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.59→40.05 Å / Num. obs: 174976 / % possible obs: 91.4 % / Redundancy: 6.9 % / Rmerge(I) obs: 0.149 / Rpim(I) all: 0.056 / Net I/σ(I): 12.7
Reflection shellResolution: 1.59→1.65 Å / Redundancy: 3.4 % / Mean I/σ(I) obs: 2 / Num. unique obs: 13524 / Rpim(I) all: 0.507 / % possible all: 80.7

-
Processing

Software
NameVersionClassification
PHENIX(1.13_2998)refinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3FPD

3fpd


Resolution: 1.591→40.049 Å / SU ML: 0.18 / Cross valid method: THROUGHOUT / σ(F): 1.33 / Phase error: 21.07
RfactorNum. reflection% reflection
Rfree0.194 3820 2.19 %
Rwork0.1807 --
obs0.1811 174575 91.06 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.591→40.049 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4142 0 268 590 5000
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0024564
X-RAY DIFFRACTIONf_angle_d0.6486165
X-RAY DIFFRACTIONf_dihedral_angle_d8.0093618
X-RAY DIFFRACTIONf_chiral_restr0.043623
X-RAY DIFFRACTIONf_plane_restr0.003788
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.5909-1.6110.278790.31784400X-RAY DIFFRACTION63
1.611-1.63220.27351540.28894833X-RAY DIFFRACTION70
1.6322-1.65460.3282910.27685025X-RAY DIFFRACTION72
1.6546-1.67820.2964680.26665298X-RAY DIFFRACTION75
1.6782-1.70320.25752120.25585307X-RAY DIFFRACTION77
1.7032-1.72990.231820.25065527X-RAY DIFFRACTION79
1.7299-1.75820.2262460.23795781X-RAY DIFFRACTION82
1.7582-1.78850.26032540.235708X-RAY DIFFRACTION84
1.7885-1.82110.24141310.2265994X-RAY DIFFRACTION86
1.8211-1.85610.2502450.22396346X-RAY DIFFRACTION90
1.8561-1.8940.22912660.22296288X-RAY DIFFRACTION93
1.894-1.93520.25181140.22926674X-RAY DIFFRACTION95
1.9352-1.98020.1949820.21936822X-RAY DIFFRACTION97
1.9802-2.02970.23972240.21096789X-RAY DIFFRACTION99
2.0297-2.08460.26331580.20596928X-RAY DIFFRACTION100
2.0846-2.14590.1897940.19836989X-RAY DIFFRACTION100
2.1459-2.21520.2262250.1926835X-RAY DIFFRACTION100
2.2152-2.29430.22471480.18466976X-RAY DIFFRACTION100
2.2943-2.38620.2262980.1846992X-RAY DIFFRACTION100
2.3862-2.49480.21941940.18346856X-RAY DIFFRACTION99
2.4948-2.62630.19542130.17946693X-RAY DIFFRACTION98
2.6263-2.79080.2754180.16967095X-RAY DIFFRACTION100
2.7908-3.00620.18312410.16526860X-RAY DIFFRACTION100
3.0062-3.30860.19511810.16116907X-RAY DIFFRACTION100
3.3086-3.7871000000000.14617104X-RAY DIFFRACTION100
3.787-4.770.13524020.13056672X-RAY DIFFRACTION100
4.77-40.06171000000000.1537056X-RAY DIFFRACTION99
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)
12.90080.3132-0.45797.71130.1592.4919-0.0443-0.2088-0.48240.27380.09420.62790.2879-0.2692-0.03570.1128-0.00950.02120.17040.04340.2418-21.3204-27.406129.497
21.1842-0.1960.09462.1185-0.47022.71250.06460.15140.079-0.0895-0.0398-0.08790.01670.1755-0.0250.06670.02830.00950.0999-0.00440.1099-12.4473-2.927610.8984
33.6121-2.00450.15575.1238-0.05592.38380.28450.3447-0.1756-0.4389-0.2162-0.21910.31320.2172-0.06210.20280.075-0.00710.1985-0.02440.0914-11.064-13.4853.1672
41.5594-2.31041.93966.7975-2.28452.44530.24170.1033-0.4252-0.0980.08860.54530.079-0.2087-0.31270.12660.0017-0.04650.1539-0.00810.1636-20.1408-16.07638.9098
51.5003-0.3268-0.07453.6315-0.43682.0376-0.0133-0.044-0.1437-0.07660.04020.01750.1289-0.0039-0.03580.07160.0249-0.02080.10050.00180.1197-11.1702-25.113122.7005
65.951-1.43642.25846.00551.67186.1331-0.18690.00690.18670.07540.1243-0.7175-0.08120.47270.02880.0990.025-0.04480.1069-0.01560.1449-3.2704-15.461727.0788
70.3845-0.48710.33954.3457-1.58810.78030.08980.0629-0.0224-0.2964-0.067-0.01760.12830.0506-0.01630.08660.0197-0.01590.122-0.02490.0878-7.3784-18.714316.4669
82.8318-0.95880.53772.0543-0.41852.61990.08750.2736-0.3156-0.2825-0.0104-0.06220.21840.1446-0.08520.16630.04180.00150.1028-0.02190.1418-3.6851-29.710418.7266
92.13411.79183.91127.91923.11887.94110.0830.1269-0.1635-0.39780.0251-0.43080.30620.3276-0.06840.18360.0730.02690.15870.00640.18273.3805-35.939922.8436
1010.0271-6.82056.312.1907-5.34787.44570.1570.5844-0.1415-0.3506-0.1240.1174-0.0833-0.1354-0.16820.2410.0399-0.04670.2343-0.04310.142-33.3741-0.34524.1651
117.55820.02754.71930.78930.04784.7721-0.0230.72620.4505-0.3702-0.0849-0.1209-0.389-0.02390.10270.2370.09450.02230.26590.04680.1057-29.11828.12945.7559
121.58850.20520.54492.5137-0.72241.53240.0989-0.3695-0.13050.3923-0.01530.1166-0.04310.0366-0.08040.16680.05910.01650.1477-0.00870.131-22.7527-5.787934.5313
133.1181-1.54990.12184.8283-0.39391.948-0.1283-0.3865-0.17570.3740.20560.5062-0.1086-0.2545-0.05570.11980.01390.04520.18590.03870.1348-35.1965-3.959633.7059
143.4489-2.61622.77034.1484-2.63032.41040.22380.1719-0.3004-0.3204-0.06380.44550.3171-0.0488-0.18830.11470.0066-0.0280.12810.00020.1871-34.5678-7.901123.4774
152.8996-0.37790.00632.2427-0.1572.10180.08750.22470.2513-0.2091-0.03830.0811-0.161-0.1942-0.02630.12180.05560.00310.12020.00880.1142-34.6588.693114.426
168.7031.799-1.06227.84660.60912.41280.0778-0.54571.0050.8023-0.0123-0.2536-0.3940.141-0.06850.22080.0366-0.00010.179-0.07760.3294-24.525916.466322.1124
171.6877-0.81880.40781.9055-0.37061.8320.003-0.05130.10450.00940.01470.1001-0.0996-0.147-0.01170.06620.00370.00540.097-0.01490.1002-33.73848.133921.0668
187.4883.11120.84586.55561.52063.26460.1546-0.07081.2696-0.0332-0.07470.1358-0.3942-0.2045-0.05720.20010.06690.03330.1579-0.00710.3686-40.127824.203518.6585
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 975 through 1011 )
2X-RAY DIFFRACTION2chain 'A' and (resid 1012 through 1042 )
3X-RAY DIFFRACTION3chain 'A' and (resid 1043 through 1082 )
4X-RAY DIFFRACTION4chain 'A' and (resid 1083 through 1096 )
5X-RAY DIFFRACTION5chain 'A' and (resid 1097 through 1136 )
6X-RAY DIFFRACTION6chain 'A' and (resid 1137 through 1163 )
7X-RAY DIFFRACTION7chain 'A' and (resid 1164 through 1197 )
8X-RAY DIFFRACTION8chain 'A' and (resid 1198 through 1219 )
9X-RAY DIFFRACTION9chain 'A' and (resid 1220 through 1235 )
10X-RAY DIFFRACTION10chain 'B' and (resid 976 through 995 )
11X-RAY DIFFRACTION11chain 'B' and (resid 996 through 1015 )
12X-RAY DIFFRACTION12chain 'B' and (resid 1016 through 1042 )
13X-RAY DIFFRACTION13chain 'B' and (resid 1043 through 1082 )
14X-RAY DIFFRACTION14chain 'B' and (resid 1083 through 1096 )
15X-RAY DIFFRACTION15chain 'B' and (resid 1097 through 1136 )
16X-RAY DIFFRACTION16chain 'B' and (resid 1137 through 1153 )
17X-RAY DIFFRACTION17chain 'B' and (resid 1154 through 1212 )
18X-RAY DIFFRACTION18chain 'B' and (resid 1213 through 1235 )

+
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