PDB-5tbh: Crystal structure of mouse CARM1 in complex with inhibitor LH1236

ID or keywords:

Entry

Database: PDB / ID: 5tbh

Title

Crystal structure of mouse CARM1 in complex with inhibitor LH1236

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

regulation of growth plate cartilage chondrocyte proliferation / histone H3R26 methyltransferase activity / histone H3R17 methyltransferase activity / endochondral bone morphogenesis / histone H3R2 methyltransferase activity / RMTs methylate histone arginines / Regulation of lipid metabolism by PPARalpha / Cytoprotection by HMOX1 / protein-arginine omega-N asymmetric methyltransferase activity / type I protein arginine methyltransferase ...
Similarity search - Function

Biological species

Mus musculus (house mouse)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.341 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

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Download

PDBx/mmCIF format	5tbh.cif.gz	791.2 KB	Display	PDBx/mmCIF format
PDB format	pdb5tbh.ent.gz	673.3 KB	Display	PDB format
PDBx/mmJSON format	5tbh.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	5tbh_validation.pdf.gz	1.6 MB	Display	wwPDB validaton report
Full document	5tbh_full_validation.pdf.gz	1.6 MB	Display
Data in XML	5tbh_validation.xml.gz	53 KB	Display
Data in CIF	5tbh_validation.cif.gz	73.8 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/tb/5tbh ftp://data.pdbj.org/pub/pdb/validation_reports/tb/5tbh	HTTPS FTP

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Related structure data

Related structure data	5lv2C 5lv3C 5lv4C 5lv5C 5tbiC 5tbjC 5ih3S S: Starting model for refinement C: citing same article (ref.)
Similar structure data	6s70-d 5ise-d 6s71-d 6s79-d 5is6-d 5k8x-d 5tbj-d 6s77-d 5tbi-d 5is9-d 6s7c-d 2y1w-d 5isg-d 5ish-d 5k8v-d 5lv3-d 5lv2-2 6s7a-d 5lv2-1 6s7b-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

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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

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

1

Idetical with deposited unit
defined by software

Unit cell

Length a, b, c (Å)	74.647, 98.529, 206.403
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	18
Space group name H-M	P2₁2₁2

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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 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
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

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Non-polymers , 6 types, 429 molecules

#2: Chemical	ChemComp-M2M / 1-METHOXY-2-(2-METHOXYETHOXY)ETHANE Mass: 134.174 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₆H₁₄O₃
#3: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 17 / Source method: obtained synthetically / Formula: C₂H₆O₂
#4: Chemical	ChemComp-PG4 / TETRAETHYLENE GLYCOL Mass: 194.226 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₈H₁₈O₅ / Comment: precipitant*YM
#5: 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
#6: Chemical	ChemComp-78K / (2~{R})-4-[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl-[[4-azanyl-1-(methoxymethyl)-2-oxidanylidene-pyrimidin-5-yl]methyl]amino]-2-azanyl-butanoic acid Mass: 534.526 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₁H₃₀N₁₀O₇
#7: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 406 / Source method: isolated from a natural source / Formula: H₂O

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.32 Å³/Da / Density % sol: 47.04 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8 Details: Tris-HCl pH 8.0 100 mM PEG 2000 MME 19% NaCl 100 mM

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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 21, 2012
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97857 Å / Relative weight: 1
Reflection	Resolution: 2.34→49.26 Å / Num. obs: 64779 / % possible obs: 99.6 % / Redundancy: 6.3 % / B_iso Wilson estimate: 30.84 Å² / CC_1/2: 0.979 / R_merge(I) obs: 0.275 / Net I/σ(I): 7.4
Reflection shell	Resolution: 2.34→2.4 Å / Redundancy: 5.9 % / R_merge(I) obs: 1.836 / Mean I/σ(I) obs: 1.8 / % possible all: 90.9

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Processing

Software

Name	Version	Classification
PHENIX	dev_1980	refinement
XDS		data reduction
XDS		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 5IH3

5ih3

Resolution: 2.341→49.26 Å / SU ML: 0.29 / Cross valid method: FREE R-VALUE / Phase error: 24.72

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.2298	6128	4.97 %	Random selection
R_work	0.1936	-	-	-
obs	0.1954	64692	99.46 %	-

Solvent computation

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

Refinement step

Cycle: LAST / Resolution: 2.341→49.26 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	10989	0	218	406	11613

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.006	11477
X-RAY DIFFRACTION	f_angle_d	1.024	15518
X-RAY DIFFRACTION	f_dihedral_angle_d	13.578	4202
X-RAY DIFFRACTION	f_chiral_restr	0.046	1692
X-RAY DIFFRACTION	f_plane_restr	0.005	2038

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 (%)
2.341-2.3676	0.3429	174	0.3106	3446	X-RAY DIFFRACTION	89
2.3676-2.3954	0.3621	176	0.2846	3996	X-RAY DIFFRACTION	100
2.3954-2.4247	0.3638	224	0.2828	3907	X-RAY DIFFRACTION	100
2.4247-2.4553	0.2764	223	0.2673	3895	X-RAY DIFFRACTION	100
2.4553-2.4877	0.2469	184	0.2494	3946	X-RAY DIFFRACTION	100
2.4877-2.5217	0.327	176	0.2479	3957	X-RAY DIFFRACTION	100
2.5217-2.5578	0.3068	236	0.2478	3860	X-RAY DIFFRACTION	100
2.5578-2.5959	0.2976	201	0.2499	3894	X-RAY DIFFRACTION	100
2.5959-2.6365	0.2514	200	0.2469	3914	X-RAY DIFFRACTION	100
2.6365-2.6797	0.2579	225	0.2334	3931	X-RAY DIFFRACTION	100
2.6797-2.7259	0.2581	181	0.2302	3906	X-RAY DIFFRACTION	100
2.7259-2.7755	0.2715	209	0.2394	3917	X-RAY DIFFRACTION	100
2.7755-2.8289	0.2982	203	0.2345	3956	X-RAY DIFFRACTION	100
2.8289-2.8866	0.2486	219	0.2293	3930	X-RAY DIFFRACTION	100
2.8866-2.9494	0.2699	167	0.2258	3926	X-RAY DIFFRACTION	100
2.9494-3.018	0.2517	216	0.231	3928	X-RAY DIFFRACTION	100
3.018-3.0934	0.2614	226	0.222	3913	X-RAY DIFFRACTION	100
3.0934-3.177	0.2346	218	0.209	3904	X-RAY DIFFRACTION	100
3.177-3.2705	0.2675	206	0.2132	3911	X-RAY DIFFRACTION	100
3.2705-3.376	0.2507	190	0.2063	3919	X-RAY DIFFRACTION	100
3.376-3.4967	0.2181	175	0.1919	3938	X-RAY DIFFRACTION	100
3.4967-3.6366	0.221	189	0.1769	3989	X-RAY DIFFRACTION	100
3.6366-3.8021	0.2093	219	0.1692	3869	X-RAY DIFFRACTION	100
3.8021-4.0025	0.1994	216	0.1562	3904	X-RAY DIFFRACTION	100
4.0025-4.2531	0.1766	246	0.1456	3898	X-RAY DIFFRACTION	100
4.2531-4.5813	0.1776	188	0.1381	3936	X-RAY DIFFRACTION	100
4.5813-5.0419	0.1744	179	0.127	3922	X-RAY DIFFRACTION	100
5.0419-5.7705	0.1994	202	0.1505	3945	X-RAY DIFFRACTION	100
5.7705-7.2665	0.1802	228	0.1794	3898	X-RAY DIFFRACTION	100
7.2665-49.2754	0.1819	232	0.1643	3861	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	0.8365	-0.4513	-0.1063	0.8851	0.1158	1.0792	0.0482	-0.0595	0.1458	0.0685	-0.0365	0.0756	-0.0848	-0.0094	0	0.1989	-0.0631	0.0371	0.1873	-0.0598	0.1862	55.0274	40.3738	132.8757
2	0.5674	0.2442	0.1936	-0.0888	-0.0142	0.2543	0.0884	-0.027	0.0278	0.0052	-0.0617	0.0282	0.0295	0.0251	0	0.1672	-0.022	0.0124	0.2071	-0.0267	0.2754	47.7684	11.9269	119.0061
3	0.7179	0.2511	-0.0406	1.0202	-0.012	0.8316	-0.0166	-0.0511	-0.045	-0.044	0.0083	-0.1041	0.0137	0.0313	-0.0001	0.19	-0.0458	0.0364	0.2472	-0.0229	0.2501	60.2283	19.3148	118.8681
4	0.5597	-0.3508	-0.4598	1.0727	0.302	1.3595	0.1451	0.054	-0.0226	-0.0724	0.0133	-0.0583	-0.1247	-0.1004	0.0163	0.202	0.0351	0.0392	0.2101	0.0296	0.2506	19.0031	19.9252	114.7517
5	0.1617	0.2559	-0.0016	0.03	-0.3473	0.3673	0.1661	-0.2171	-0.1017	0.2984	-0.0707	0.046	-0.0014	0.0189	0	0.3833	-0.0464	0.0954	0.4116	-0.0327	0.3866	38.338	29.4404	148.0175
6	0.2497	-0.1363	0.0279	0.2294	0.454	0.7947	0.129	-0.0169	0.1621	-0.0072	-0.0577	0.0335	0.1631	-0.1641	-0.0012	0.2414	-0.0044	0.0473	0.3545	0.0289	0.3589	17.175	22.061	137.4448
7	0.5125	-0.154	-0.2119	0.038	0.5268	1.1274	0.0988	-0.1227	-0.0606	0.0497	0.0176	0.0615	-0.0238	-0.0851	0.0079	0.2848	-0.0034	0.0368	0.3035	0.039	0.2538	17.0813	22.8036	139.8267
8	0.1598	-0.1711	0.2207	0.1852	-0.294	0.3261	-0.0206	-0.1055	0.2585	0.0306	-0.043	-0.4328	-0.0896	0.0645	-0.0002	0.3557	-0.0091	0.0953	0.3892	-0.02	0.4064	24.521	30.3995	141.4196
9	1.1136	0.2272	-0.7009	0.5806	-0.3729	1.2928	0.0426	0.0849	0.175	-0.0009	0.0064	0.0174	-0.1065	0.0473	0	0.3172	0.0429	0.0118	0.2983	0.0135	0.2954	23.0106	42.4707	174.9554
10	0.2095	-0.0732	0.3142	0.4405	-0.2458	0.1216	0.0723	0.0274	-0.0835	0.0003	-0.0236	0.0948	-0.0008	-0.0452	-0.0001	0.3277	0.0406	0.0325	0.2848	0.0006	0.2901	26.0209	21.2176	190.2381
11	0.6827	-0.2125	-0.21	1.065	-0.2518	0.2566	0.0205	0.0601	-0.0982	0.0687	-0.0521	0.1742	0.009	-0.0023	-0.0007	0.3062	0.0514	0.0476	0.2893	-0.0293	0.3359	16.2147	20.2755	190.222
12	0.7475	0.4116	-0.6312	0.9609	-0.3979	0.7443	0.0918	-0.0804	-0.0611	0.0118	-0.0827	-0.0105	-0.0592	0.0246	-0.0002	0.3195	0.0092	-0.0028	0.2641	-0.0167	0.2878	57.1778	18.1227	195.1103
13	0.3365	-0.475	-0.2531	-0.0033	0.1892	0.2023	0.1887	0.3169	-0.1343	-0.2483	-0.1169	0.0061	0.0898	-0.05	-0	0.409	0.0147	0.045	0.4368	-0.0374	0.3373	39.6293	28.5049	163.2755
14	0.1707	-0.0364	-0.043	0.195	-0.4442	0.6409	-0.1874	0.121	-0.0114	-0.1916	0.0845	-0.028	-0.1904	0.5092	-0.0004	0.3936	0.0444	0.0585	0.3879	0.0103	0.3937	63.5075	23.5544	174.7884
15	0.2454	0.2064	0.1241	0.1694	-0.073	0.495	-0.0859	0.1157	-0.1725	-0.0303	-0.0854	-0.0869	0.1004	0.0275	0	0.3969	0.0375	0.0504	0.347	-0.0409	0.3115	58.2439	17.851	169.4114
16	0.1069	-0.1199	0.2604	0.21	0.3842	0.5118	-0.0784	0.2108	-0.1237	0.1147	-0.1726	0.134	-0.0472	-0.2066	-0.0659	0.3508	0.0258	0.0795	0.4152	-0.0439	0.3155	54.6931	30.3646	168.12

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)

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