[English] 日本語
Yorodumi
- PDB-6s7a: Crystal structure of CARM1 in complex with inhibitor AA175 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6s7a
TitleCrystal structure of CARM1 in complex with inhibitor AA175
ComponentsHistone-arginine methyltransferase CARM1
KeywordsTRANSFERASE / Inhibitor / Complex / Arginine methyltransferase
Function / homology
Function and homology information


histone H3R17 methyltransferase activity / histone H3R2 methyltransferase activity / type I protein arginine methyltransferase / negative regulation of dendrite development / protein-arginine omega-N asymmetric methyltransferase activity / histone arginine N-methyltransferase activity / protein methyltransferase activity / regulation of intracellular estrogen receptor signaling pathway / replication fork reversal / protein-arginine N-methyltransferase activity ...histone H3R17 methyltransferase activity / histone H3R2 methyltransferase activity / type I protein arginine methyltransferase / negative regulation of dendrite development / protein-arginine omega-N asymmetric methyltransferase activity / histone arginine N-methyltransferase activity / protein methyltransferase activity / regulation of intracellular estrogen receptor signaling pathway / replication fork reversal / protein-arginine N-methyltransferase activity / positive regulation of epithelial cell apoptotic process / positive regulation of transcription by RNA polymerase I / histone methyltransferase activity / nuclear replication fork / positive regulation of fat cell differentiation / response to cAMP / RORA activates gene expression / Regulation of lipid metabolism by PPARalpha / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / BMAL1:CLOCK,NPAS2 activates circadian gene expression / Activation of gene expression by SREBF (SREBP) / nuclear receptor coactivator activity / lysine-acetylated histone binding / Heme signaling / Transcriptional activation of mitochondrial biogenesis / PPARA activates gene expression / Cytoprotection by HMOX1 / beta-catenin binding / RMTs methylate histone arginines / Transcriptional regulation of white adipocyte differentiation / Circadian Clock / DNA-binding transcription factor binding / Estrogen-dependent gene expression / methylation / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / positive regulation of cell population proliferation / regulation of DNA-templated transcription / nucleoplasm / nucleus / cytosol / cytoplasm
Similarity search - Function
Histone-arginine methyltransferase CARM1, N-terminal / Coactivator-associated arginine methyltransferase 1 N terminal / Ribosomal protein L11 methyltransferase (PrmA) / Hnrnp arginine n-methyltransferase1 / Hnrnp arginine n-methyltransferase1 / Arginine methyltransferase oligomerization subdomain / Protein arginine N-methyltransferase / SAM-dependent methyltransferase PRMT-type domain profile. / Distorted Sandwich / PH-like domain superfamily ...Histone-arginine methyltransferase CARM1, N-terminal / Coactivator-associated arginine methyltransferase 1 N terminal / Ribosomal protein L11 methyltransferase (PrmA) / Hnrnp arginine n-methyltransferase1 / Hnrnp arginine n-methyltransferase1 / Arginine methyltransferase oligomerization subdomain / Protein arginine N-methyltransferase / SAM-dependent methyltransferase PRMT-type domain profile. / Distorted Sandwich / PH-like domain superfamily / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Mainly Beta
Similarity search - Domain/homology
Chem-KY5 / Histone-arginine methyltransferase CARM1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.86 Å
AuthorsGunnell, E.A. / Al-Noori, A. / Dowden, J. / Dreveny, I.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Medical Research Council (United Kingdom)1501569 United Kingdom
CitationJournal: Biochem.J. / Year: 2020
Title: Structural and biochemical evaluation of bisubstrate inhibitors of protein arginine N-methyltransferases PRMT1 and CARM1 (PRMT4).
Authors: Gunnell, E.A. / Al-Noori, A. / Muhsen, U. / Davies, C.C. / Dowden, J. / Dreveny, I.
History
DepositionJul 4, 2019Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 4, 2020Provider: repository / Type: Initial release
Revision 1.1Mar 11, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2May 15, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone-arginine methyltransferase CARM1
B: Histone-arginine methyltransferase CARM1
C: Histone-arginine methyltransferase CARM1
D: Histone-arginine methyltransferase CARM1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)162,47714
Polymers160,0944
Non-polymers2,38310
Water12,394688
1
A: Histone-arginine methyltransferase CARM1
C: Histone-arginine methyltransferase CARM1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)81,1466
Polymers80,0472
Non-polymers1,0994
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4040 Å2
ΔGint-26 kcal/mol
Surface area26070 Å2
MethodPISA
2
B: Histone-arginine methyltransferase CARM1
D: Histone-arginine methyltransferase CARM1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)81,3308
Polymers80,0472
Non-polymers1,2836
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4570 Å2
ΔGint-29 kcal/mol
Surface area25830 Å2
MethodPISA
Unit cell
Length a, b, c (Å)74.784, 98.624, 207.137
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Components on special symmetry positions
IDModelComponents
11B-777-

HOH

Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11(chain A and (resid 135 through 303 or resid 305...
21(chain B and (resid 135 through 303 or resid 305...
31(chain C and (resid 135 through 303 or resid 305...
41(chain D and (resid 135 through 303 or resid 305...

NCS domain segments:

Ens-ID: 1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11SERSERTYRTYR(chain A and (resid 135 through 303 or resid 305...AA135 - 3031 - 169
12GLUGLULEULEU(chain A and (resid 135 through 303 or resid 305...AA305 - 426171 - 292
13ALAALAASPASP(chain A and (resid 135 through 303 or resid 305...AA428 - 432294 - 298
14LEULEUTHRTHR(chain A and (resid 135 through 303 or resid 305...AA434 - 437300 - 303
15LEULEUTYRTYR(chain A and (resid 135 through 303 or resid 305...AA439 - 476305 - 342
21SERSERTYRTYR(chain B and (resid 135 through 303 or resid 305...BB135 - 3031 - 169
22GLUGLULEULEU(chain B and (resid 135 through 303 or resid 305...BB305 - 426171 - 292
23ALAALAASPASP(chain B and (resid 135 through 303 or resid 305...BB428 - 432294 - 298
24LEULEUTHRTHR(chain B and (resid 135 through 303 or resid 305...BB434 - 437300 - 303
25LEULEUTYRTYR(chain B and (resid 135 through 303 or resid 305...BB439 - 476305 - 342
31SERSERTYRTYR(chain C and (resid 135 through 303 or resid 305...CC135 - 3031 - 169
32GLUGLULEULEU(chain C and (resid 135 through 303 or resid 305...CC305 - 426171 - 292
33ALAALAASPASP(chain C and (resid 135 through 303 or resid 305...CC428 - 432294 - 298
34LEULEUTHRTHR(chain C and (resid 135 through 303 or resid 305...CC434 - 437300 - 303
35LEULEUTYRTYR(chain C and (resid 135 through 303 or resid 305...CC439 - 476305 - 342
41SERSERTYRTYR(chain D and (resid 135 through 303 or resid 305...DD135 - 3031 - 169
42GLUGLULEULEU(chain D and (resid 135 through 303 or resid 305...DD305 - 426171 - 292
43ALAALAASPASP(chain D and (resid 135 through 303 or resid 305...DD428 - 432294 - 298
44LEULEUTHRTHR(chain D and (resid 135 through 303 or resid 305...DD434 - 437300 - 303
45LEULEUTYRTYR(chain D and (resid 135 through 303 or resid 305...DD439 - 476305 - 342

-
Components

#1: Protein
Histone-arginine methyltransferase CARM1 / Coactivator-associated arginine methyltransferase 1 / Protein arginine N-methyltransferase 4


Mass: 40023.484 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CARM1, PRMT4 / Production host: Escherichia coli (E. coli)
References: UniProt: Q86X55, type I protein arginine methyltransferase
#2: Chemical
ChemComp-KY5 / (2~{R},3~{R},4~{S},5~{R})-2-(6-aminopurin-9-yl)-5-[[3-azanylpropyl-[3-(pyridin-2-ylamino)propyl]amino]methyl]oxolane-3,4-diol


Mass: 457.529 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H31N9O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C3H8O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 688 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.39 Å3/Da / Density % sol: 48.44 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 0.1 M Bis-tris propane, 0.2 M sodium formate, 20 % (w/v) PEG 3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.976 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jul 8, 2017
RadiationMonochromator: Si (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.976 Å / Relative weight: 1
ReflectionResolution: 1.86→71.422 Å / Num. obs: 129298 / % possible obs: 100 % / Redundancy: 6.6 % / Biso Wilson estimate: 34.73 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.095 / Rpim(I) all: 0.04 / Rrim(I) all: 0.103 / Net I/σ(I): 9.1
Reflection shell

Diffraction-ID: 1 / % possible all: 100

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) all
1.86-1.895.31.82963290.3930.8762.032
10.19-71.4225.60.0549310.9940.0250.06

-
Processing

Software
NameVersionClassification
PHENIXrefinement
Aimless0.5.32data scaling
PDB_EXTRACT3.24data extraction
XDSdata reduction
PHASERphasing
RefinementResolution: 1.86→71.422 Å / SU ML: 0.22 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 23.84
RfactorNum. reflection% reflectionSelection details
Rfree0.2199 6444 4.99 %RANDOM
Rwork0.1993 ---
obs0.2004 129154 99.93 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 97.46 Å2 / Biso mean: 44.8777 Å2 / Biso min: 19.87 Å2
Refinement stepCycle: final / Resolution: 1.86→71.422 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10976 0 168 688 11832
Biso mean--50.38 47.73 -
Num. residues----1368
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A6541X-RAY DIFFRACTION8.137TORSIONAL
12B6541X-RAY DIFFRACTION8.137TORSIONAL
13C6541X-RAY DIFFRACTION8.137TORSIONAL
14D6541X-RAY DIFFRACTION8.137TORSIONAL
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 30

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.86-1.88110.35711980.351440754273100
1.8811-1.90330.38611990.324940484247100
1.9033-1.92650.34372190.315240134232100
1.9265-1.95090.28692100.301540224232100
1.9509-1.97650.29422320.284240704302100
1.9765-2.00360.28262110.28240244235100
2.0036-2.03220.27372080.269540824290100
2.0322-2.06260.28612120.266340604272100
2.0626-2.09480.27262290.259940304259100
2.0948-2.12920.27052290.247740254254100
2.1292-2.16590.23322240.242740464270100
2.1659-2.20530.24681900.232841014291100
2.2053-2.24770.26422310.231840574288100
2.2477-2.29360.26221970.22940704267100
2.2936-2.34340.26491930.226241014294100
2.3434-2.3980.24212090.221240164225100
2.398-2.45790.23952160.221640894305100
2.4579-2.52440.2582210.217540984319100
2.5244-2.59870.2462090.213240724281100
2.5987-2.68260.24462000.21240824282100
2.6826-2.77840.21782500.206340494299100
2.7784-2.88970.2222260.198640994325100
2.8897-3.02120.2182390.199740864325100
3.0212-3.18050.19872180.199641054323100
3.1805-3.37970.22582110.19241004311100
3.3797-3.64070.19791970.17741714368100
3.6407-4.0070.20682210.17141254346100
4.007-4.58680.17062030.156342034406100
4.5868-5.77850.18412170.163342274444100
5.7785-71.47440.19292250.1874364458999
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)
12.4671-0.4890.12021.5051-0.47121.7711-0.0418-0.1149-0.2171-0.05910.07440.08880.4264-0.1461-0.01670.7342-0.1345-0.04330.60440.01890.3944-14.05777.1274-71.7251
20.77270.4224-0.36150.9389-0.35670.7970.0784-0.06280.02380.0024-0.04860.21130.2815-0.298-0.02390.5422-0.1095-0.05530.5257-0.01180.3497-14.828726.7867-86.5289
31.16870.66950.14472.3307-0.23490.57530.0663-0.10640.1253-0.1465-0.11760.2858-0.0273-0.20740.06340.5698-0.1017-0.09920.602-0.06090.373-20.931830.1682-88.022
41.78960.3045-0.0421.63950.3551.99030.04320.2458-0.2334-0.1702-0.09590.13850.1606-0.09910.06130.29470.0711-0.0410.2794-0.07860.302317.34929.2407-30.0315
50.9704-0.1699-0.25950.05010.08110.50060.09640.00120.0732-0.055-0.0384-0.00660.02910.0673-0.0670.22070.0147-0.02170.2045-0.00760.30799.869535.7239-14.8191
61.0628-0.0668-0.00662.67150.2411.067-0.03260.0343-0.03-0.0099-0.0085-0.22860.07010.16260.03340.20270.0572-0.04770.3044-0.03240.26923.887227.2608-17.8842
70.8586-0.46570.16942.66220.50251.58530.0332-0.02540.02720.0399-0.0523-0.0796-0.10910.05910.00570.19390.0256-0.04190.2331-0.00410.253622.120932.0269-15.4427
81.4426-0.16390.64281.7982-0.36111.72190.16970.0676-0.0686-0.0199-0.0821-0.12820.21420.2352-0.08370.58290.0886-0.00920.5279-0.04010.332918.635831.1366-92.7599
91.19690.56450.35730.30580.10430.14810.2335-0.28370.10690.1481-0.1367-0.0228-0.02960.0097-0.06690.59820.0421-0.0470.6021-0.03970.39057.773122.2725-64.9596
100.8435-0.0582-0.56090.6847-1.04812.78190.0108-0.08260.0087-0.0976-0.0540.04290.0030.21210.05040.54670.0388-0.09660.571-0.06090.36120.015426.3943-67.1841
111.17420.39210.36391.31430.57292.18450.1452-0.0716-0.1131-0.0230.0288-0.06020.2191-0.0349-0.15610.246-0.0498-0.05310.20410.03840.2948-17.254429.7748-11.053
121.6567-0.51820.50230.38970.00820.28060.3150.5163-0.114-0.2018-0.19160.03940.06670.1076-0.09980.37570.0271-0.0770.3710.00450.3077-5.963321.9211-38.8437
132.62740.5147-0.75521.31260.62712.80230.09950.1198-0.1533-0.0308-0.10020.0531-0.0313-0.0056-0.01640.28390.0183-0.09990.2869-0.00710.3335-20.517126.0908-33.1476
141.30530.023-0.40610.92640.60732.41930.08230.3208-0.0451-0.1538-0.0089-0.07260.1562-0.009-0.08490.3334-0.0148-0.08050.35530.04110.313-19.438525.7826-37.03
151.92770.8316-0.13522.26880.41962.63440.21760.0578-0.05750.1072-0.2208-0.36210.17510.0656-0.03240.45370.086-0.07240.46660.00230.4453-11.303320.7087-40.1632
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 135 through 252 )A135 - 252
2X-RAY DIFFRACTION2chain 'A' and (resid 253 through 368 )A253 - 368
3X-RAY DIFFRACTION3chain 'A' and (resid 369 through 476 )A369 - 476
4X-RAY DIFFRACTION4chain 'B' and (resid 135 through 278 )B135 - 278
5X-RAY DIFFRACTION5chain 'B' and (resid 279 through 335 )B279 - 335
6X-RAY DIFFRACTION6chain 'B' and (resid 336 through 368 )B336 - 368
7X-RAY DIFFRACTION7chain 'B' and (resid 369 through 476 )B369 - 476
8X-RAY DIFFRACTION8chain 'C' and (resid 135 through 278 )C135 - 278
9X-RAY DIFFRACTION9chain 'C' and (resid 279 through 335 )C279 - 335
10X-RAY DIFFRACTION10chain 'C' and (resid 336 through 476 )C336 - 476
11X-RAY DIFFRACTION11chain 'D' and (resid 135 through 278 )D135 - 278
12X-RAY DIFFRACTION12chain 'D' and (resid 279 through 335 )D279 - 335
13X-RAY DIFFRACTION13chain 'D' and (resid 336 through 368 )D336 - 368
14X-RAY DIFFRACTION14chain 'D' and (resid 369 through 456 )D369 - 456
15X-RAY DIFFRACTION15chain 'D' and (resid 457 through 476 )D457 - 476

+
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