PDB-7vrh: crystal structure of BRD2-BD1 in complex with guanosine analog

ID or keywords:

Entry

Database: PDB / ID: 7vrh

Title

crystal structure of BRD2-BD1 in complex with guanosine analog

Components

Bromodomain-containing protein 2

Keywords

TRANSCRIPTION/INHIBITOR / BET family / BET inhibitor / Bromodomain Inhibitor / BRD2-BD1 inhibitor / TRANSCRIPTION-INHIBITOR COMPLEX

Function / homology

Function and homology information

acetylation-dependent protein binding / chromatin looping / RUNX3 regulates p14-ARF / positive regulation of T-helper 17 cell lineage commitment / protein localization to chromatin / neural tube closure / lysine-acetylated histone binding / nucleosome assembly / spermatogenesis / histone binding ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

MOLECULAR REPLACEMENT / Resolution: 2.2 Å

Authors

Padmanabhan, B. / Arole, A. / Deshmukh, P. / Ashok, S. / Mathur, S.

Funding support

1items

Citation

Journal: Acta Crystallogr D Struct Biol / Year: 2023
Title: Structural and biochemical insights into purine-based drug molecules in hBRD2 delineate a unique binding mode opening new vistas in the design of inhibitors of the BET family.
Authors: Arole, A.H. / Deshmukh, P. / Sridhar, A. / Mathur, S. / Mahalingaswamy, M. / Subramanya, H. / Dalavaikodihalli Nanjaiah, N. / Padmanabhan, B.

History

Deposition	Oct 22, 2021	Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0	Feb 1, 2023	Provider: repository / Type: Initial release
Revision 1.1	Aug 2, 2023	Group: Database references / Category: citation / citation_author Item: _citation.journal_abbrev / _citation.journal_id_CSD ..._citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2	Aug 16, 2023	Group: Data collection / Database references Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	7vrh.cif.gz	158.4 KB	Display	PDBx/mmCIF format
PDB format	pdb7vrh.ent.gz	124.2 KB	Display	PDB format
PDBx/mmJSON format	7vrh.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	7vrh_validation.pdf.gz	1.2 MB	Display	wwPDB validaton report
Full document	7vrh_full_validation.pdf.gz	1.2 MB	Display
Data in XML	7vrh_validation.xml.gz	16.6 KB	Display
Data in CIF	7vrh_validation.cif.gz	23 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/vr/7vrh ftp://data.pdbj.org/pub/pdb/validation_reports/vr/7vrh	HTTPS FTP

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Related structure data

Related structure data	7vriC 7vrkC 7vrmC 7vroC 7vrqC 7vrzC 7vs0C 7vs1C 7vsfC 6jkeS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	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	#92 - Aug 2007 Anabolic Steroids similarity (1) #127 - Jul 2010 Crystallins similarity (1) #174 - Jun 2014 GFP-like Proteins similarity (1) #89 - May 2007 Aconitase and Iron Regulatory Protein 1 similarity (1) #122 - Feb 2010 Enhanceosome similarity (1)

Deposited unit

A: Bromodomain-containing protein 2

B: Bromodomain-containing protein 2

C: Bromodomain-containing protein 2

hetero molecules

44.1 kDa, 3 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Bromodomain-containing protein 2

B: Bromodomain-containing protein 2

hetero molecules

defined by author&software
Evidence: gel filtration
29.5 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

C: Bromodomain-containing protein 2

hetero molecules

C: Bromodomain-containing protein 2

hetero molecules

defined by author&software
29.1 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	113.083, 55.473, 67.792
Angle α, β, γ (deg.)	90.00, 94.15, 90.00
Int Tables number	5
Space group name H-M	C121
Symmetry operation	#1: x,y,z #2: -x,y,-z #3: x+1/2,y+1/2,z #4: -x+1/2,y+1/2,-z

#1: Protein	Bromodomain-containing protein 2 / O27.1.1 / Really interesting new gene 3 protein Mass: 14471.866 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRD2, KIAA9001, RING3 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: P25440
#2: Chemical	ChemComp-AC2 / 9-HYROXYETHOXYMETHYLGUANINE Mass: 225.205 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₈H₁₁N₅O₃ / Feature type: SUBJECT OF INVESTIGATION / Comment: medication, antivirus*YM
#3: Chemical	ChemComp-DTT / 2,3-DIHYDROXY-1,4-DITHIOBUTANE / 1,4-DITHIOTHREITOL Mass: 154.251 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₄H₁₀O₂S₂
#4: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO₄
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 160 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.44 Å³/Da / Density % sol: 49.64 %
Crystal grow	Temperature: 300 K / Method: vapor diffusion, hanging drop / Details: PEG MME 5000, 0.8M Ammonium sulfate

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5406 Å
Detector	Type: RIGAKU HyPix-6000HE / Detector: PIXEL / Date: Aug 28, 2020
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.5406 Å / Relative weight: 1
Reflection	Resolution: 2.2→50 Å / Num. obs: 20793 / % possible obs: 97 % / Redundancy: 4 % / B_iso Wilson estimate: 29.4 Å² / CC_1/2: 1 / R_merge(I) obs: 0.118 / Net I/σ(I): 18.51
Reflection shell	Resolution: 2.2→2.24 Å / Redundancy: 2 % / R_merge(I) obs: 0.406 / Mean I/σ(I) obs: 2 / Num. unique obs: 884 / CC_1/2: 0.78 / % possible all: 81.4

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Processing

Software

Name	Version	Classification
PHENIX	(1.18_3855: ???)	refinement
HKL-3000		data reduction
HKL-3000		data scaling
PHENIX		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 6jke

6jke

Resolution: 2.2→28.39 Å / SU ML: 0.31 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 28.86 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.2409	1039	5 %
R_work	0.1927	-	-
obs	0.1951	20793	96.85 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL

Refinement step

Cycle: LAST / Resolution: 2.2→28.39 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	2747	0	21	160	2928

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.008	2860
X-RAY DIFFRACTION	f_angle_d	0.94	3871
X-RAY DIFFRACTION	f_dihedral_angle_d	5.906	398
X-RAY DIFFRACTION	f_chiral_restr	0.05	405
X-RAY DIFFRACTION	f_plane_restr	0.006	512

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 (%)
2.2-2.32	0.3944	118	0.3596	2476	X-RAY DIFFRACTION	86
2.32-2.46	0.2598	154	0.2383	2757	X-RAY DIFFRACTION	96
2.46-2.65	0.2815	157	0.2095	2870	X-RAY DIFFRACTION	99
2.65-2.92	0.2835	143	0.2177	2878	X-RAY DIFFRACTION	99
2.92-3.34	0.257	157	0.2047	2885	X-RAY DIFFRACTION	99
3.34-4.2	0.2127	155	0.1637	2923	X-RAY DIFFRACTION	100
4.21-28.39	0.2016	155	0.1588	2965	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	0.3468	0.0164	0.0815	0.2106	-0.0476	0.0845	0.0561	-0.5972	-0.8496	0.1808	0.0937	1.2224	-0.144	-0.0228	0.0064	0.4529	0.1296	0.1214	0.6403	0.2198	0.6658	3.5478	5.4366	81.9125
2	0.3745	-0.3343	0.0522	0.2919	0.1781	0.2104	-0.1146	0.0145	0.0349	-0.0332	-0.0892	0.2921	-0.0624	-0.3224	0.0008	0.34	0.0554	0.0562	0.3099	0.0268	0.3732	6.0783	14.9552	70.3618
3	0.4633	0.6223	-0.0719	0.8368	-0.3033	0.4196	0.0802	0.4408	-0.2353	-0.5937	-0.3786	0.533	0.0077	-0.3119	0.0001	0.4149	0.0009	-0.0426	0.4186	-0.0462	0.3801	11.2608	7.2032	55.7343
4	0.4479	0.1647	0.1576	0.3669	0.0506	0.0753	-0.3681	0.2251	-0.7675	-0.206	-0.0545	0.1493	0.9755	0.0301	0.0048	0.4685	0.0283	-0.0106	0.3088	-0.0147	0.4526	16.5841	-0.6057	60.0546
5	0.1938	-0.0125	-0.1455	0.063	0.0771	0.1352	-0.4101	-0.047	-0.5617	0.3811	0.5007	0.9842	0.0883	-0.9964	-0.0012	0.2864	0.0147	0.1585	0.3864	0.0241	0.5507	3.2419	2.8173	69.6707
6	0.0468	-0.1715	-0.0579	0.8699	0.3403	0.1402	-0.3818	-0.7241	-1.1085	1.5826	0.1973	1.1345	0.6082	-0.3299	-0.0059	0.6612	0.0362	0.3602	0.5468	0.1634	0.9671	3.8538	-3.9585	76.7552
7	3.2512	-2.26	0.555	2.6769	0.5599	1.0213	-0.3036	-0.3033	0.0109	-0.0143	0.1698	0.2092	0.1919	0.0267	0.0001	0.2828	-0.0017	0.0118	0.2335	-0.0128	0.3077	17.7002	6.0645	67.2384
8	0.7286	-0.2682	0.1754	0.3918	-0.0637	0.1398	-0.1502	-0.2003	0.0839	0.3202	-0.0716	0.0988	-0.7014	0.3406	-0.0017	0.3542	0.0352	0.0499	0.3097	-0.0038	0.3145	15.7634	14.6721	71.9366
9	0.1592	-0.1549	-0.2124	0.1686	0.2148	0.2568	-0.1899	-0.6112	-1.1538	0.7203	-0.5467	0.5328	0.7449	-1.0104	-0.0105	0.8924	-0.0863	0.0656	0.6109	0.1678	0.5664	7.7802	2.9419	88.3981
10	1.1969	0.5346	0.539	1.2564	-0.4265	0.6807	-0.0484	-0.5663	0.1143	0.4206	0.1984	-0.1646	0.0415	0.1216	-0.0009	0.4973	0.055	-0.0584	0.4091	-0.007	0.3159	29.0072	4.683	85.522
11	0.4204	-0.0775	0.179	0.1294	-0.0013	0.088	0.3427	0.5435	0.3267	-0.4055	-1.0222	-1.0574	0.0989	1.3284	-0.0037	0.4604	0.0978	0.0402	0.6035	0.0711	0.5931	41.4681	9.8842	69.9934
12	1.924	-0.009	0.9859	2.3288	-0.767	2.1152	-0.0576	-0.2336	0.1582	0.1793	0.1031	-0.183	-0.431	0.0841	0	0.354	-0.0101	-0.0499	0.2691	-0.0042	0.3737	29.6788	13.2008	76.1591
13	0.3939	0.1947	0.3232	1.2659	-0.5481	0.5062	-0.1446	0.1569	-0.3399	-0.0114	0.0493	0.195	0.2526	-0.4117	-0.0001	0.3619	-0.0266	-0.0136	0.2769	0.0275	0.3454	24.265	1.0678	76.7017
14	0.0181	-0.0116	0.0299	0.0836	-0.0728	0.0638	0.7453	-0.2634	0.6955	0.6274	0.1911	0.4932	-0.2394	-0.1609	-0.0024	0.6786	0.0819	0.1523	0.7528	-0.1827	0.6396	14.7758	11.7823	92.007
15	0.1042	0.1155	0.0284	0.1448	-0.0089	0.0631	-0.6363	0.2084	1.098	0.391	0.1736	-0.2958	-1.5905	0.2353	-0.0008	0.6118	0.0415	0.007	0.4763	0.1093	0.4914	-7.1724	34.063	90.132
16	0.0144	0.0888	-0.0145	0.2406	0.1371	-0.0448	-0.3647	0.5464	0.1277	-0.6664	0.4779	0.0608	-0.1026	0.7557	0.0123	0.3361	0.0745	0.1154	0.5095	-0.003	0.3657	1.703	20.9007	88.0092
17	0.0867	-0.2744	-0.0426	0.2704	0.0834	0.1511	-0.186	0.0978	-0.7119	0.016	0.049	-0.3351	0.6088	0.0581	0.0006	0.6351	0.0569	0.0361	0.4592	-0.07	0.4765	-7.4296	6.7001	84.8052
18	0.0149	0.0268	-0.0694	0.327	0.0896	0.1773	0.0584	0.2454	0.1077	-0.7691	0.1664	0.649	0.2851	-0.5254	-0.0001	0.4262	0.0652	-0.0639	0.4595	-0.0196	0.379	-14.7416	9.0074	90.9891
19	0.1113	0.0264	-0.0121	0.1495	0.0191	0.0176	-0.1248	0.6144	0.5854	-1.4542	0.096	0.1667	0.4934	0.0777	-0.0013	0.4671	-0.0091	-0.0014	0.4645	0.0646	0.3626	-9.8482	23.6327	84.0637
20	0.9288	0.7701	-0.3542	0.5192	0.0945	2.109	-0.0445	-0.067	0.0331	-0.2846	0.2485	0.2278	-0.1447	-0.2422	0.0001	0.3455	0.0557	-0.0101	0.4279	0.0055	0.2822	-11.9327	20.9228	93.1602
21	0.2359	0.1251	0.0494	0.0556	0.0449	0.3139	-0.1862	0.565	-0.9976	-0.6338	-0.2163	-0.6928	0.6482	0.2784	0.0035	0.5408	0.1375	-0.0339	0.3559	-0.057	0.5957	-1.1474	3.4101	97.8515
22	2.3085	1.4817	-0.0188	1.0801	-0.2985	2.0567	-0.1889	0.18	0.2518	0.5188	0.2669	-0.2634	-0.1131	0.4914	-0.0008	0.3177	0.0038	0.0359	0.4706	0.0005	0.3184	-1.003	22.1732	97.8297

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid 75 through 84 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 85 through 96 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 97 through 112 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 113 through 122 )
5	X-RAY DIFFRACTION	5	chain 'A' and (resid 123 through 131 )
6	X-RAY DIFFRACTION	6	chain 'A' and (resid 132 through 137 )
7	X-RAY DIFFRACTION	7	chain 'A' and (resid 138 through 160 )
8	X-RAY DIFFRACTION	8	chain 'A' and (resid 161 through 179 )
9	X-RAY DIFFRACTION	9	chain 'A' and (resid 180 through 186 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 76 through 99 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 100 through 112 )
12	X-RAY DIFFRACTION	12	chain 'B' and (resid 113 through 160 )
13	X-RAY DIFFRACTION	13	chain 'B' and (resid 161 through 179 )
14	X-RAY DIFFRACTION	14	chain 'B' and (resid 180 through 185 )
15	X-RAY DIFFRACTION	15	chain 'C' and (resid 76 through 84 )
16	X-RAY DIFFRACTION	16	chain 'C' and (resid 85 through 98 )
17	X-RAY DIFFRACTION	17	chain 'C' and (resid 99 through 112 )
18	X-RAY DIFFRACTION	18	chain 'C' and (resid 113 through 122 )
19	X-RAY DIFFRACTION	19	chain 'C' and (resid 123 through 131 )
20	X-RAY DIFFRACTION	20	chain 'C' and (resid 132 through 155 )
21	X-RAY DIFFRACTION	21	chain 'C' and (resid 156 through 160 )
22	X-RAY DIFFRACTION	22	chain 'C' and (resid 161 through 182 )

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