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- PDB-5lv3: Crystal structure of mouse CARM1 in complex with ligand LH1561Br -

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Basic information

Entry
Database: PDB / ID: 5lv3
TitleCrystal structure of mouse CARM1 in complex with ligand LH1561Br
ComponentsHistone-arginine methyltransferase CARM1
KeywordsTRANSFERASE / PROTEIN ARGININE METHYLTRANSFERASE / CATALYTIC DOMAIN / CHROMATIN REGULATOR / MRNA PROCESSING / MRNA SPLICING / NUCLEUS / S-ADENOSYL-L-METHIONINE / TRANSCRIPTION / TRANSCRIPTION REGULATION
Function / homology
Function and homology information


histone H3R26 methyltransferase activity / regulation of growth plate cartilage chondrocyte proliferation / histone H3R17 methyltransferase activity / endochondral bone morphogenesis / histone H3R2 methyltransferase activity / RMTs methylate histone arginines / Regulation of lipid metabolism by PPARalpha / negative regulation of dendrite development / type I protein arginine methyltransferase / Cytoprotection by HMOX1 ...histone H3R26 methyltransferase activity / regulation of growth plate cartilage chondrocyte proliferation / histone H3R17 methyltransferase activity / endochondral bone morphogenesis / histone H3R2 methyltransferase activity / RMTs methylate histone arginines / Regulation of lipid metabolism by PPARalpha / negative regulation of dendrite development / type I protein arginine methyltransferase / Cytoprotection by HMOX1 / protein-arginine omega-N asymmetric methyltransferase activity / protein methyltransferase activity / Estrogen-dependent gene expression / histone arginine N-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 / intracellular estrogen receptor signaling pathway / intracellular steroid hormone receptor signaling pathway / response to cAMP / protein localization to chromatin / nuclear receptor coactivator activity / lysine-acetylated histone binding / RNA polymerase II transcription regulator complex / methylation / DNA-binding transcription factor binding / cell population proliferation / transcription coactivator activity / transcription cis-regulatory region binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / 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 / Protein arginine N-methyltransferase / SAM-dependent methyltransferase PRMT-type domain profile. / Vaccinia Virus protein VP39 / 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 / Protein arginine N-methyltransferase / SAM-dependent methyltransferase PRMT-type domain profile. / Vaccinia Virus protein VP39 / Distorted Sandwich / PH-like domain superfamily / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Rossmann fold / 3-Layer(aba) Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
Chem-LHF / S-ADENOSYL-L-HOMOCYSTEINE / Histone-arginine methyltransferase CARM1
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsCura, V. / Marechal, N. / Troffer-Charlier, N. / Halby, L. / Arimondo, P. / Bonnefond, L. / Cavarelli, J.
CitationJournal: Philos. Trans. R. Soc. Lond., B, Biol. Sci. / Year: 2018
Title: Hijacking DNA methyltransferase transition state analogues to produce chemical scaffolds for PRMT inhibitors.
Authors: Halby, L. / Marechal, N. / Pechalrieu, D. / Cura, V. / Franchini, D.M. / Faux, C. / Alby, F. / Troffer-Charlier, N. / Kudithipudi, S. / Jeltsch, A. / Aouadi, W. / Decroly, E. / Guillemot, J. ...Authors: Halby, L. / Marechal, N. / Pechalrieu, D. / Cura, V. / Franchini, D.M. / Faux, C. / Alby, F. / Troffer-Charlier, N. / Kudithipudi, S. / Jeltsch, A. / Aouadi, W. / Decroly, E. / Guillemot, J.C. / Page, P. / Ferroud, C. / Bonnefond, L. / Guianvarc'h, D. / Cavarelli, J. / Arimondo, P.B.
History
DepositionSep 12, 2016Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 20, 2017Provider: repository / Type: Initial release
Revision 1.1May 2, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_abbrev / _citation.journal_id_ASTM ..._citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.name
Revision 1.2Jan 17, 2024Group: 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

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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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)165,3768
Polymers163,4024
Non-polymers1,9744
Water20,2851126
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area9120 Å2
ΔGint-57 kcal/mol
Surface area50860 Å2
MethodPISA
Unit cell
Length a, b, c (Å)75.092, 98.524, 208.097
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21212

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Components

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


Mass: 40850.457 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Carm1, Prmt4 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q9WVG6, type I protein arginine methyltransferase
#2: Chemical ChemComp-SAH / S-ADENOSYL-L-HOMOCYSTEINE / S-Adenosyl-L-homocysteine


Type: L-peptide linking / Mass: 384.411 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C14H20N6O5S
#3: Chemical ChemComp-LHF / 5-[[2-[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]ethylamino]methyl]-4-azanyl-1-[2-(4-bromanylphenoxy)ethyl]pyrimidin-2-one


Mass: 602.440 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C24H28BrN9O5
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 1126 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.36 Å3/Da / Density % sol: 47.78 %
Crystal growTemperature: 297 K / Method: vapor diffusion, hanging drop / pH: 8
Details: Tris-HCl pH 8.0 100 mM PEG 2000 MME 15% NaCl 100 mM

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-2 / Wavelength: 0.8726 Å
DetectorType: DECTRIS PILATUS 2M-F / Detector: PIXEL / Date: Nov 11, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.8726 Å / Relative weight: 1
ReflectionResolution: 1.8→30 Å / Num. obs: 143500 / % possible obs: 100 % / Redundancy: 7.9 % / Biso Wilson estimate: 21.8 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.156 / Net I/σ(I): 8.7
Reflection shellResolution: 1.8→1.82 Å / Redundancy: 7.9 % / Rmerge(I) obs: 1.867 / Mean I/σ(I) obs: 1.1 / CC1/2: 0.302 / % possible all: 100

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Processing

Software
NameVersionClassification
PHENIX(dev_2386: ???)refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5IH3
Resolution: 1.8→29.992 Å / SU ML: 0.19 / Cross valid method: FREE R-VALUE / Phase error: 19.89
RfactorNum. reflection% reflectionSelection details
Rfree0.203 7112 4.96 %Random selection
Rwork0.1735 ---
obs0.175 143435 99.97 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 30.85 Å2
Refinement stepCycle: LAST / Resolution: 1.8→29.992 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10985 0 130 1126 12241
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00511405
X-RAY DIFFRACTIONf_angle_d0.81415460
X-RAY DIFFRACTIONf_dihedral_angle_d13.856754
X-RAY DIFFRACTIONf_chiral_restr0.0491687
X-RAY DIFFRACTIONf_plane_restr0.0042027
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.8-1.82050.34062550.31534498X-RAY DIFFRACTION100
1.8205-1.84190.28482120.2874476X-RAY DIFFRACTION100
1.8419-1.86430.28392190.28874519X-RAY DIFFRACTION100
1.8643-1.88790.33662210.28014526X-RAY DIFFRACTION100
1.8879-1.91280.28322680.26144451X-RAY DIFFRACTION100
1.9128-1.9390.29392330.24624512X-RAY DIFFRACTION100
1.939-1.96670.2722140.23464527X-RAY DIFFRACTION100
1.9667-1.9960.22962380.22694476X-RAY DIFFRACTION100
1.996-2.02720.26392460.21724507X-RAY DIFFRACTION100
2.0272-2.06040.23612510.20514465X-RAY DIFFRACTION100
2.0604-2.09590.22462250.19914523X-RAY DIFFRACTION100
2.0959-2.1340.23782190.18624538X-RAY DIFFRACTION100
2.134-2.17510.22792460.18564496X-RAY DIFFRACTION100
2.1751-2.21950.23552470.17794501X-RAY DIFFRACTION100
2.2195-2.26770.21482480.17074498X-RAY DIFFRACTION100
2.2677-2.32040.20092140.17084523X-RAY DIFFRACTION100
2.3204-2.37840.21392220.16684561X-RAY DIFFRACTION100
2.3784-2.44270.18662510.17234510X-RAY DIFFRACTION100
2.4427-2.51460.20082280.16424562X-RAY DIFFRACTION100
2.5146-2.59570.20462410.16494527X-RAY DIFFRACTION100
2.5957-2.68840.18232420.15784527X-RAY DIFFRACTION100
2.6884-2.7960.19552250.15484551X-RAY DIFFRACTION100
2.796-2.92310.19342290.15874555X-RAY DIFFRACTION100
2.9231-3.07710.17872360.16454577X-RAY DIFFRACTION100
3.0771-3.26960.19872420.16194582X-RAY DIFFRACTION100
3.2696-3.52170.18832280.15744589X-RAY DIFFRACTION100
3.5217-3.87550.17262460.14664593X-RAY DIFFRACTION100
3.8755-4.43470.14982600.13194627X-RAY DIFFRACTION100
4.4347-5.58140.16462270.13384683X-RAY DIFFRACTION100
5.5814-29.99640.20612790.19294843X-RAY DIFFRACTION100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
10.7283-0.27030.17710.7620.05321.28780.0074-0.12210.11610.1442-0.06270.0793-0.0867-0.04310.06620.17-0.06130.03090.1575-0.06170.13755.148940.1504134.1754
20.58810.19050.37320.04180.13590.30640.0842-0.059-0.08090.0081-0.0389-0.0335-0.01620.0443-0.04850.0897-0.01960.00780.1038-0.01070.163947.451713.8606118.9094
30.43390.2897-0.05891.45780.07090.83390.0053-0.0259-0.0757-0.0062-0.0077-0.07220.03440.03750.00850.0886-0.02910.02690.1199-0.01570.117260.14518.658120.3497
43.8122-1.16190.21793.81870.79691.47970.12060.07210.3042-0.23680.1802-0.2792-0.43250.2186-0.14180.2601-0.02040.10860.1718-0.01870.223528.56832.8613118.9499
51.4969-0.44870.06360.15730.03381.00150.189-0.0282-0.03620.08670.0165-0.08470.03060.0699-0.14210.14080.01560.00330.1114-0.02490.163123.110410.2549121.7356
61.09450.2941-0.70921.6407-0.26320.92410.09630.1105-0.0783-0.0216-0.0213-0.0168-0.0162-0.1767-0.03990.11290.03160.00890.15270.02890.153314.387114.6421111.1303
70.8779-0.64640.01410.75960.14690.88840.17450.20810.076-0.1715-0.0657-0.0217-0.1172-0.1246-0.10570.13750.03290.01570.12350.03180.148321.071319.3963106.4212
80.4720.0767-0.42180.4944-0.16471.01890.1390.00750.10680.0463-0.04140.0288-0.1856-0.1349-0.12590.14140.03330.03350.13380.03450.15614.982423.7008125.7344
91.71790.88960.2060.480.0740.04370.1544-0.2187-0.17230.2946-0.11490.0178-0.0064-0.1117-0.04180.2956-0.07040.0740.3419-0.03120.202942.053830.8063149.5829
101.3165-0.13870.34210.87790.26251.47710.1531-0.1320.10580.05-0.06240.04630.0324-0.0629-0.05830.1662-0.01790.05870.18290.01310.167516.979623.3969137.2966
110.89430.02710.14960.30220.39821.20590.1499-0.2769-0.0080.161-0.0178-0.04890.064-0.0296-0.11050.2034-0.03230.02540.20170.0330.151517.304720.0233141.8414
120.7360.20970.36080.7144-0.25460.98710.154-0.23710.1952-0.0087-0.027-0.1063-0.11820.1218-0.09490.2015-0.01990.05410.2378-0.02330.181723.10231.1392141.9416
131.33930.2478-0.44270.721-0.18141.2981-0.04020.10070.1128-0.03820.03390.0388-0.12-0.00920.00840.24280.05230.00530.21990.01840.142322.683341.5175178.1743
140.8476-0.14680.3720.4662-0.22090.47840.10750.0321-0.18010.0209-0.05220.18670.0066-0.0182-0.04630.16980.00610.0150.1386-0.00780.15528.738914.6919193.6329
151.0166-0.42740.03681.2712-0.43630.4954-0.00050.067-0.25920.02280.01330.31660.0094-0.0904-0.01350.22960.03330.03310.2546-0.01210.272413.682620.655188.9878
161.17830.33150.29231.4460.15280.5959-0.0824-0.0159-0.13510.2154-0.02210.2460.06310.0280.12690.28510.03450.0910.23390.00080.238221.432719.9757197.9869
171.16140.4155-0.25571.3714-0.48671.13410.0658-0.131-0.02210.1067-0.0391-0.1509-0.0650.0105-0.03590.1737-0.011-0.00640.164-0.01420.133555.558716.6849198.8374
180.26120.0527-0.01540.1992-0.05480.98820.05460.0629-0.0209-0.0408-0.0682-0.0719-0.1280.0018-0.00380.23690.02220.01630.1977-0.01820.185661.761821.8281186.5798
191.4593-0.93630.28950.64-0.14430.08760.1990.3861-0.1779-0.3717-0.1304-0.0716-0.08280.1042-0.00190.35740.04970.07510.4371-0.00460.222535.334831.4617162.846
200.6989-0.05270.37730.4676-0.77631.29630.06090.2644-0.1015-0.1225-0.0720.01830.11540.08910.02050.28560.05260.04670.2842-0.03930.18959.196319.5784171.8621
210.3664-0.11490.43260.55830.24290.7697-0.04290.2389-0.05060.1192-0.05280.0523-0.0038-0.10230.06680.31080.04890.05690.3537-0.00730.189154.535230.5572170.2156
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 136 through 279 )
2X-RAY DIFFRACTION2chain 'A' and (resid 280 through 336 )
3X-RAY DIFFRACTION3chain 'A' and (resid 337 through 478 )
4X-RAY DIFFRACTION4chain 'B' and (resid 135 through 155 )
5X-RAY DIFFRACTION5chain 'B' and (resid 156 through 179 )
6X-RAY DIFFRACTION6chain 'B' and (resid 180 through 217 )
7X-RAY DIFFRACTION7chain 'B' and (resid 218 through 253 )
8X-RAY DIFFRACTION8chain 'B' and (resid 254 through 300 )
9X-RAY DIFFRACTION9chain 'B' and (resid 301 through 336 )
10X-RAY DIFFRACTION10chain 'B' and (resid 337 through 369 )
11X-RAY DIFFRACTION11chain 'B' and (resid 370 through 433 )
12X-RAY DIFFRACTION12chain 'B' and (resid 434 through 477 )
13X-RAY DIFFRACTION13chain 'C' and (resid 136 through 279 )
14X-RAY DIFFRACTION14chain 'C' and (resid 280 through 337 )
15X-RAY DIFFRACTION15chain 'C' and (resid 338 through 433 )
16X-RAY DIFFRACTION16chain 'C' and (resid 434 through 477 )
17X-RAY DIFFRACTION17chain 'D' and (resid 136 through 253 )
18X-RAY DIFFRACTION18chain 'D' and (resid 254 through 300 )
19X-RAY DIFFRACTION19chain 'D' and (resid 301 through 336 )
20X-RAY DIFFRACTION20chain 'D' and (resid 337 through 433 )
21X-RAY DIFFRACTION21chain 'D' and (resid 434 through 476 )

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