PDB-5tbi: Crystal structure of mouse CARM1 in complex with inhibitor LH1427

ID or keywords:

Entry

Database: PDB / ID: 5tbi

Title

Crystal structure of mouse CARM1 in complex with inhibitor LH1427

Components

Histone-arginine methyltransferase CARM1

Keywords

TRANSFERASE / 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 / type I protein arginine methyltransferase / negative regulation of dendrite development / protein-arginine omega-N asymmetric methyltransferase activity ...
Similarity search - Function

Biological species

Mus musculus (house mouse)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.294 Å

Authors

Cura, V. / Marechal, N. / Troffer-Charlier, N. / Halby, L. / Arimondo, P. / Bonnefond, L. / Cavarelli, J.

Citation

Journal: 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. ...

History

Deposition	Sep 12, 2016	Deposition site: RCSB / Processing site: PDBE
Revision 1.0	Sep 20, 2017	Provider: repository / Type: Initial release
Revision 1.1	Apr 3, 2019	Group: Data collection / Database references / Category: citation / citation_author / pdbx_database_proc Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _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
Revision 1.2	Jan 17, 2024	Group: 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 viewer	Molecule: MolmilJmol/JSmol

-
Download

PDBx/mmCIF format	5tbi.cif.gz	797.2 KB	Display	PDBx/mmCIF format
PDB format	pdb5tbi.ent.gz	678.9 KB	Display	PDB format
PDBx/mmJSON format	5tbi.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

-
Validation report

Summary document	5tbi_validation.pdf.gz	1.6 MB	Display	wwPDB validaton report
Full document	5tbi_full_validation.pdf.gz	1.6 MB	Display
Data in XML	5tbi_validation.xml.gz	55.2 KB	Display
Data in CIF	5tbi_validation.cif.gz	76.9 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/tb/5tbi ftp://data.pdbj.org/pub/pdb/validation_reports/tb/5tbi	HTTPS FTP

-
Related structure data

Related structure data	5lv2C 5lv3C 5lv4C 5lv5C 5tbhC 5tbjC 5ih3S S: Starting model for refinement C: citing same article (ref.)
Similar structure data	5lv2-1 5lv3-d 6s7a-d 5isa-d 5dwq-d 6s77-d 5is6-d 5u4x-d 5isc-d 6s71-d 6s7b-d 2y1w-d 5is7-d 5k8x-d 5tbj-d 6s79-d 5tbh-d 5k8v-d 5ish-d 6s70-d Search similar-shape structures by Omokage search (details) Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

-
Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#122 - Feb 2010 Enhanceosome similarity (3) #155 - Nov 2012 Vitamin D Receptor similarity (2) #63 - Mar 2005 T-Cell Receptor similarity (1)

Deposited unit

A: Histone-arginine methyltransferase CARM1

B: Histone-arginine methyltransferase CARM1

C: Histone-arginine methyltransferase CARM1

D: Histone-arginine methyltransferase CARM1

hetero molecules

166 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software

Unit cell

Length a, b, c (Å)	74.494, 98.029, 205.730
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	18
Space group name H-M	P2₁2₁2

Components on special symmetry positions

ID	Model	Components
1	1	A-506- EDO

-
Protein , 1 types, 4 molecules ABCD

#1: Protein	Histone-arginine methyltransferase CARM1 / Coactivator-associated arginine methyltransferase 1 / Protein arginine N-methyltransferase 4 Mass: 40850.457 Da / Num. of mol.: 4 / Fragment: UNP residues 130-487 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

#1: Protein

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

Mass: 40850.457 Da / Num. of mol.: 4 / Fragment: UNP residues 130-487
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

-
Non-polymers , 5 types, 622 molecules

#2: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 17 / Source method: obtained synthetically / Formula: C₂H₆O₂
#3: Chemical	ChemComp-SAO / 5'-S-[(3S)-3-azaniumyl-3-carboxypropyl]-5'-thioadenosine / S-ADENOSYL-L-HOMOCYSTEINE Type: L-peptide linking / Mass: 385.419 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₄H₂₁N₆O₅S
#4: Chemical	ChemComp-PE8 / 3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL Mass: 370.436 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₆H₃₄O₉
#5: Chemical	ChemComp-78V / 4-[2-[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methylamino]ethylamino]-1-(methoxymethyl)pyrimidin-2-one Mass: 447.448 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₁₈H₂₅N₉O₅
#6: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 600 / Source method: isolated from a natural source / Formula: H₂O

-
Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

Crystal	Density Matthews: 2.3 Å³/Da / Density % sol: 46.49 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8 Details: Tris-HCl pH 8.0 100 mM PEG 2000 MME 21% NaCl 100 mM

-
Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.97857 Å
Detector	Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 17, 2014
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97857 Å / Relative weight: 1
Reflection	Resolution: 2.29→49.01 Å / Num. obs: 67916 / % possible obs: 99.3 % / Redundancy: 4.4 % / B_iso Wilson estimate: 31.25 Å² / CC_1/2: 0.991 / R_merge(I) obs: 0.163 / Net I/σ(I): 6.9
Reflection shell	Resolution: 2.29→2.35 Å / Redundancy: 4.1 % / R_merge(I) obs: 1.152 / Mean I/σ(I) obs: 1.2 / % possible all: 92.3

-
Processing

Software

Name	Version	Classification
PHENIX	dev_1951	refinement
XDS		data reduction
XDS		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 5IH3

5ih3

Resolution: 2.294→45.544 Å / SU ML: 0.32 / Cross valid method: FREE R-VALUE / Phase error: 24.44

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.2284	6469	5 %	Random selection
R_work	0.1977	-	-	-
obs	0.1993	67860	99.31 %	-

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å

Refinement step

Cycle: LAST / Resolution: 2.294→45.544 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	10989	0	209	600	11798

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.004	11470
X-RAY DIFFRACTION	f_angle_d	0.855	15502
X-RAY DIFFRACTION	f_dihedral_angle_d	14.346	4201
X-RAY DIFFRACTION	f_chiral_restr	0.04	1690
X-RAY DIFFRACTION	f_plane_restr	0.004	2036

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
2.2942-2.3203	0.3426	199	0.3357	3654	X-RAY DIFFRACTION	87
2.3203-2.3476	0.3272	209	0.316	4130	X-RAY DIFFRACTION	100
2.3476-2.3762	0.3336	197	0.3059	4113	X-RAY DIFFRACTION	100
2.3762-2.4063	0.3986	256	0.3098	4101	X-RAY DIFFRACTION	100
2.4063-2.4379	0.2761	223	0.2855	4049	X-RAY DIFFRACTION	100
2.4379-2.4713	0.3077	204	0.2948	4204	X-RAY DIFFRACTION	100
2.4713-2.5066	0.3749	181	0.2818	4129	X-RAY DIFFRACTION	100
2.5066-2.544	0.2941	223	0.2784	4071	X-RAY DIFFRACTION	100
2.544-2.5838	0.2892	231	0.2713	4164	X-RAY DIFFRACTION	100
2.5838-2.6261	0.268	208	0.2735	4097	X-RAY DIFFRACTION	100
2.6261-2.6714	0.3209	238	0.2573	4101	X-RAY DIFFRACTION	100
2.6714-2.72	0.2924	191	0.2451	4151	X-RAY DIFFRACTION	100
2.72-2.7723	0.2809	223	0.2473	4105	X-RAY DIFFRACTION	100
2.7723-2.8289	0.286	212	0.2461	4068	X-RAY DIFFRACTION	100
2.8289-2.8904	0.288	225	0.2436	4150	X-RAY DIFFRACTION	100
2.8904-2.9576	0.2516	180	0.2338	4168	X-RAY DIFFRACTION	100
2.9576-3.0315	0.2569	226	0.216	4084	X-RAY DIFFRACTION	100
3.0315-3.1135	0.2498	249	0.2121	4052	X-RAY DIFFRACTION	99
3.1135-3.2051	0.2228	200	0.1963	4138	X-RAY DIFFRACTION	100
3.2051-3.3085	0.1967	205	0.1917	4115	X-RAY DIFFRACTION	100
3.3085-3.4267	0.2188	206	0.1887	4164	X-RAY DIFFRACTION	100
3.4267-3.5639	0.2192	191	0.1769	4133	X-RAY DIFFRACTION	100
3.5639-3.726	0.1996	221	0.1625	4147	X-RAY DIFFRACTION	100
3.726-3.9223	0.1912	244	0.1576	4076	X-RAY DIFFRACTION	100
3.9223-4.1679	0.17	220	0.138	4080	X-RAY DIFFRACTION	100
4.1679-4.4895	0.1681	230	0.134	4085	X-RAY DIFFRACTION	100
4.4895-4.9408	0.1625	183	0.1225	4204	X-RAY DIFFRACTION	100
4.9408-5.6546	0.1739	218	0.1425	4103	X-RAY DIFFRACTION	100
5.6546-7.1198	0.1768	228	0.1828	4101	X-RAY DIFFRACTION	100
7.1198-45.5534	0.1938	248	0.1763	4068	X-RAY DIFFRACTION	99

Refinement TLS params.

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

ID	L11 (°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)
1	1.0475	-0.2447	0.2403	0.9625	0.2193	0.983	0.0355	-0.0802	0.1076	0.0696	-0.0506	0.0495	-0.0266	0.0307	0.0002	0.202	-0.0529	0.0418	0.1886	-0.0672	0.197	55.0054	40.1872	132.4924
2	0.6869	0.2219	0.0442	-0.1859	-0.0358	0.0604	0.0744	-0.0239	0.0148	0.0576	-0.0556	0.0504	0.056	0.0489	0.0019	0.2024	-0.0162	0.0157	0.2118	-0.0144	0.2929	47.7318	11.8681	118.5675
3	0.2853	0.3835	0.0089	1.403	0.3567	0.7644	-0.0036	-0.0358	-0.0367	-0.0561	0.0069	-0.0601	0.0446	0.0155	0	0.165	-0.0385	0.0424	0.2227	-0.0086	0.2381	60.1498	19.2108	118.4744
4	0.1525	-0.0449	-0.5452	0.9692	0.2463	1.2497	0.1151	0.0874	0.0004	-0.0298	0.0007	-0.0185	-0.1266	-0.0904	0.0164	0.1978	0.0391	0.0294	0.2048	0.0244	0.2643	18.9644	19.8626	114.3525
5	0.3912	0.1832	-0.3096	0.0115	-0.0836	0.4647	0.1471	-0.3342	-0.0445	0.1741	-0.0562	0.0406	0.0174	0.0315	0.0025	0.3472	-0.0099	0.08	0.4147	-0.0011	0.3266	38.3987	29.3444	147.6467
6	0.311	-0.1147	-0.1406	0.4043	0.5519	0.6823	0.0715	-0.0294	0.0952	0.077	-0.149	0.0814	0.1611	-0.0603	-0.0003	0.26	0.0149	0.0711	0.3301	0.0397	0.3379	17.1482	21.8938	137.0302
7	0.4622	-0.0745	-0.0289	-0.0726	0.1085	1.2963	0.0802	-0.1309	-0.053	0.0452	-0.0154	0.0442	-0.0182	-0.0635	0.0017	0.2506	0.0164	0.043	0.2501	0.0269	0.232	17.0288	22.6233	139.4155
8	0.2666	-0.0011	0.3952	0.3159	0.028	0.4448	0.0169	-0.2497	0.1239	-0.0305	-0.1281	-0.2794	-0.1226	0.2877	-0.0698	0.2997	0.016	0.0869	0.3725	0.0141	0.3742	24.5404	30.3066	140.9535
9	1.4731	0.2576	-0.6225	0.4907	-0.7037	1.0699	-0.0141	0.206	0.1404	0.0117	0.0151	-0.0053	-0.0883	0.0597	-0	0.3751	0.0487	0.0018	0.3243	-0.0012	0.2729	22.9067	42.2892	174.3542
10	0.3506	-0.1989	0.382	0.2719	-0.2018	0.1513	0.0804	-0.0793	-0.0576	-0.0185	-0.0043	0.0661	0.0017	-0.0455	-0	0.3637	0.0326	0.0214	0.3008	0.0081	0.3041	25.9298	21.1134	189.6508
11	0.4679	-0.1078	-0.2349	1.2155	-0.2871	0.1494	-0.0256	0.0405	-0.1243	0.0895	-0.0325	0.1599	-0.037	0.0542	-0.0108	0.3482	0.0578	0.0696	0.3284	-0.0229	0.3399	16.1361	20.1742	189.6006
12	0.7901	0.1493	-0.5255	1.0955	-0.3932	0.6802	0.1202	-0.0425	-0.0685	0.0325	-0.1174	-0.0906	-0.0909	-0.0032	0	0.3344	-0.017	-0.0061	0.2826	-0.0226	0.2779	57.0288	18.0497	194.4889
13	0.5671	-0.6973	-0.1491	0.3111	0.2547	-0.0084	0.0523	0.2831	-0.032	-0.1144	-0.0864	-0.1108	0.0008	-0.0781	-0.0004	0.4059	-0.0042	0.0749	0.5423	-0.0612	0.368	39.4726	28.4068	162.6235
14	0.3774	-0.1548	0.0577	0.4423	-0.5141	0.5398	-0.2554	0.2217	-0.0605	-0.0121	0.0303	-0.1365	-0.0263	0.503	-0.0015	0.3985	0.0134	0.0398	0.4472	-0.004	0.3564	63.3476	23.3147	174.2304
15	0.3338	0.1074	0.1766	0.0509	-0.1093	0.5995	-0.0446	0.0943	-0.1361	-0.0551	-0.1133	-0.0461	0.179	0.0169	-0	0.4233	0.019	0.0606	0.3928	-0.0489	0.3446	58.1248	17.6765	168.8133
16	-0.0098	0.021	0.2	0.2676	0.2607	0.4848	-0.0343	0.2759	-0.1942	0.083	-0.2681	0.1319	-0.2051	-0.2324	-0.0872	0.3897	0.0533	0.0452	0.4354	-0.0618	0.3123	54.5957	30.1549	167.5291

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	(chain A and resid 136:282)
2	X-RAY DIFFRACTION	2	(chain A and resid 283:349)
3	X-RAY DIFFRACTION	3	(chain A and resid 350:478)
4	X-RAY DIFFRACTION	4	(chain B and resid 135:293)
5	X-RAY DIFFRACTION	5	(chain B and resid 294:336)
6	X-RAY DIFFRACTION	6	(chain B and resid 337:365)
7	X-RAY DIFFRACTION	7	(chain B and resid 366:445)
8	X-RAY DIFFRACTION	8	(chain B and resid 446:477)
9	X-RAY DIFFRACTION	9	(chain C and resid 136:257)
10	X-RAY DIFFRACTION	10	(chain C and resid 258:336)
11	X-RAY DIFFRACTION	11	(chain C and resid 337:478)
12	X-RAY DIFFRACTION	12	(chain D and resid 136:293)
13	X-RAY DIFFRACTION	13	(chain D and resid 294:344)
14	X-RAY DIFFRACTION	14	(chain D and resid 345:372)
15	X-RAY DIFFRACTION	15	(chain D and resid 373:430)
16	X-RAY DIFFRACTION	16	(chain D and resid 431:476)

-
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

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
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

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Related structure data

-
Links

-
Assembly

-
Components

-
Protein , 1 types, 4 molecules ABCD

-
Non-polymers , 5 types, 622 molecules

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi

-Movie

-Structure viewers

+Viewer log

-This page

-This web site

-Options

+Open data

-Basic information

-Structure visualization

-Downloads & links

-Download

-Validation report

-Related structure data

-Links

-Assembly

-Components

-Protein , 1 types, 4 molecules ABCD

-Non-polymers , 5 types, 622 molecules

-Experimental details

-Experiment

-Sample preparation

-Data collection

-Processing

+About Yorodumi

-News

-Feb 9, 2022. New format data for meta-information of EMDB entries

-Aug 12, 2020. Covid-19 info

+Mar 5, 2020. Novel coronavirus structure data

+Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+Jul 12, 2017. Major update of PDB

-Yorodumi

-
Movie

-
Structure viewers

+
Viewer log

-
This page

-
This web site

-
Options

+
Open data

-
Basic information

-
Structure visualization

-
Downloads & links

-
Download

-
Validation report

-
Related structure data

-
Links

-
Assembly

-
Components

-
Protein , 1 types, 4 molecules ABCD

-
Non-polymers , 5 types, 622 molecules

-
Experimental details

-
Experiment

-
Sample preparation

-
Data collection

-
Processing

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

-
Aug 12, 2020. Covid-19 info

+
Mar 5, 2020. Novel coronavirus structure data

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

+
Jul 12, 2017. Major update of PDB

-
Yorodumi