PDB-5d3n: First bromodomain of BRD4 bound to inhibitor XD40

ID or keywords:

Entry

Database: PDB / ID: 5d3n

Title

First bromodomain of BRD4 bound to inhibitor XD40

Components

Bromodomain-containing protein 4

Keywords

TRANSCRIPTION / Gene regulation / Bromodomain / Inhibitor

Function / homology

Function and homology information

RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / positive regulation of T-helper 17 cell lineage commitment / positive regulation of G2/M transition of mitotic cell cycle / histone reader activity / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

MOLECULAR REPLACEMENT / Resolution: 2.15 Å

Authors

Wohlwend, D. / Huegle, M.

Funding support

Germany, 1items

Citation

Journal: J.Med.Chem. / Year: 2016
Title: 4-Acyl Pyrrole Derivatives Yield Novel Vectors for Designing Inhibitors of the Acetyl-Lysine Recognition Site of BRD4(1).
Authors: Hugle, M. / Lucas, X. / Weitzel, G. / Ostrovskyi, D. / Breit, B. / Gerhardt, S. / Einsle, O. / Gunther, S. / Wohlwend, D.

History

Deposition	Aug 6, 2015	Deposition site: RCSB / Processing site: PDBE
Revision 1.0	Jan 20, 2016	Provider: repository / Type: Initial release
Revision 1.1	Mar 9, 2016	Group: Database references
Revision 1.2	Sep 6, 2017	Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3	May 8, 2024	Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2 Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	5d3n.cif.gz	71 KB	Display	PDBx/mmCIF format
PDB format	pdb5d3n.ent.gz	52.3 KB	Display	PDB format
PDBx/mmJSON format	5d3n.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	5d3n_validation.pdf.gz	733.8 KB	Display	wwPDB validaton report
Full document	5d3n_full_validation.pdf.gz	734.4 KB	Display
Data in XML	5d3n_validation.xml.gz	7.9 KB	Display
Data in CIF	5d3n_validation.cif.gz	10.1 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/d3/5d3n ftp://data.pdbj.org/pub/pdb/validation_reports/d3/5d3n	HTTPS FTP

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Related structure data

Related structure data	5d24C 5d25C 5d26C 5d3hC 5d3jC 5d3lC 5d3pC 5d3rC 5d3sC 5d3tC C: citing same article (ref.)
Similar structure data	5hq5-d 6prt-d 5dx4-d 6dl2-d 4mr3-d 5acy-2 5d24-d 6saj-d 6g0p-d 4hbv-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

Deposited unit

A: Bromodomain-containing protein 4

hetero molecules

15.4 kDa, 1 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)	39.080, 43.500, 79.110
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	19
Space group name H-M	P2₁2₁2₁

#1: Protein	Bromodomain-containing protein 4 / Protein HUNK1 Mass: 15012.301 Da / Num. of mol.: 1 / Fragment: First bromodomain, UNP residues 44-168 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Production host: Escherichia coli (E. coli) / References: UniProt: O60885
#2: Chemical	ChemComp-L40 / 4-acetyl-3-ethyl-5-methyl-N-[2-methyl-5-(methylsulfamoyl)phenyl]-1H-pyrrole-2-carboxamide Mass: 377.458 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₈H₂₃N₃O₄S
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 62 / Source method: isolated from a natural source / Formula: H₂O

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Experiment

Experiment	Method: X-RAY DIFFRACTION

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Sample preparation

Crystal	Density Matthews: 2.24 Å³/Da / Density % sol: 45.08 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: Tacsimate

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å
Detector	Type: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Jan 18, 2013
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.5418 Å / Relative weight: 1
Reflection	Resolution: 2→43.5 Å / Num. obs: 9604 / % possible obs: 99.8 % / Redundancy: 4 % / R_merge(I) obs: 0.081 / Net I/σ(I): 9.5
Reflection shell	Resolution: 2→2.11 Å / R_merge(I) obs: 0.512 / Mean I/σ(I) obs: 2.4 / Num. unique all: 1368 / % possible all: 100

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0071	refinement
SCALA	3.3.21	data scaling
PHASER	2.5.6	phasing
iMOSFLM		data reduction

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.15→39.55 Å / Cor.coef. F_o:F_c: 0.948 / Cor.coef. F_o:F_c free: 0.933 / SU B: 16.302 / SU ML: 0.211 / Cross valid method: THROUGHOUT / ESU R: 0.327 / ESU R Free: 0.214 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.23496	764	9.9 %	RANDOM
R_work	0.20832	-	-	-
obs	0.21102	6975	99.65 %	-

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK

Displacement parameters

B_iso mean: 40.812 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	3.93 Å²	-0 Å²	0 Å²
2-	-	-1.74 Å²	-0 Å²
3-	-	-	-2.19 Å²

Refinement step

Cycle: 1 / Resolution: 2.15→39.55 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1056	0	26	62	1144

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.01	0.02	1131
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.02	1074
X-RAY DIFFRACTION	r_angle_refined_deg	1.322	1.997	1546
X-RAY DIFFRACTION	r_angle_other_deg	0.789	3	2481
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	5.525	5	129
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	35.529	26	55
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	16.776	15	199
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	13.604	15	3
X-RAY DIFFRACTION	r_chiral_restr	0.065	0.2	161
X-RAY DIFFRACTION	r_gen_planes_refined	0.006	0.021	1281
X-RAY DIFFRACTION	r_gen_planes_other	0.006	0.02	256
X-RAY DIFFRACTION	r_nbd_refined
X-RAY DIFFRACTION	r_nbd_other
X-RAY DIFFRACTION	r_nbtor_refined
X-RAY DIFFRACTION	r_nbtor_other
X-RAY DIFFRACTION	r_xyhbond_nbd_refined
X-RAY DIFFRACTION	r_xyhbond_nbd_other
X-RAY DIFFRACTION	r_metal_ion_refined
X-RAY DIFFRACTION	r_metal_ion_other
X-RAY DIFFRACTION	r_symmetry_vdw_refined
X-RAY DIFFRACTION	r_symmetry_vdw_other
X-RAY DIFFRACTION	r_symmetry_hbond_refined
X-RAY DIFFRACTION	r_symmetry_hbond_other
X-RAY DIFFRACTION	r_symmetry_metal_ion_refined
X-RAY DIFFRACTION	r_symmetry_metal_ion_other
X-RAY DIFFRACTION	r_mcbond_it	1.111	2.419	513
X-RAY DIFFRACTION	r_mcbond_other	1.105	2.414	512
X-RAY DIFFRACTION	r_mcangle_it	1.703	3.623	643
X-RAY DIFFRACTION	r_mcangle_other	1.702	3.628	644
X-RAY DIFFRACTION	r_scbond_it	1.061	2.51	618
X-RAY DIFFRACTION	r_scbond_other	1.06	2.511	619
X-RAY DIFFRACTION	r_scangle_it
X-RAY DIFFRACTION	r_scangle_other	1.641	3.744	904
X-RAY DIFFRACTION	r_long_range_B_refined	4.21	22.898	4812
X-RAY DIFFRACTION	r_long_range_B_other	4.152	22.794	4768
X-RAY DIFFRACTION	r_rigid_bond_restr
X-RAY DIFFRACTION	r_sphericity_free
X-RAY DIFFRACTION	r_sphericity_bonded

LS refinement shell

Resolution: 2.15→2.206 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.454	49	-
R_work	0.308	509	-
obs	-	-	100 %

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	6.17	-1.4284	1.1119	0.447	-0.2148	4.7989	0.1255	-0.1593	0.1384	0.1471	0.1011	-0.1128	-0.4165	-0.3937	-0.2265	0.3407	0.0695	-0.0748	0.1093	-0.0389	0.0808	-14.5441	8.9128	15.7204
2	0.1476	1.0472	0.0042	9.6614	-1.6208	1.2301	0.0448	-0.0315	0.0042	0.2814	0.0253	0.1452	0.0632	-0.1827	-0.0701	0.1527	-0.043	-0.0031	0.1243	0.0076	0.1792	-14.6208	-6.0668	27.0579
3	6.3512	-0.8425	-1.2201	8.6556	3.6582	4.628	0.1469	-0.1479	0.0489	0.8169	0.063	-0.4128	0.7895	0.8465	-0.2098	0.3543	0.0927	-0.0155	0.2524	0.0674	0.3002	-7.2853	-14.4333	15.67
4	2.0272	-2.7389	1.2718	10.7152	2.1557	7.6066	0.0209	-0.0159	-0.405	-0.026	0.084	-0.5808	0.4698	0.6346	-0.105	0.048	0.045	0.0738	0.1417	0.081	0.3927	-4.1918	-2.8478	4.0114
5	7.1479	0.7564	3.4251	1.921	0.0986	4.7917	-0.2741	0.6785	0.1537	-0.0272	0.3833	-0.1714	-0.6287	-0.0595	-0.1092	0.0926	0.0335	0.0369	0.1633	0.0232	0.0698	-13.9706	13.0136	3.3182
6	5.7045	-2.2119	1.7015	2.3596	-2.2935	2.3386	-0.1467	-0.0116	0.1068	0.0837	0.1174	-0.0557	-0.1037	-0.1983	0.0293	0.092	0.0033	-0.0032	0.1339	0.0046	0.0817	-18.2367	4.7282	8.391
7	7.6269	-6.5227	2.311	5.5886	-1.9335	9.1337	-0.0542	-0.4055	0.551	0.0663	0.307	-0.508	0.11	0.4019	-0.2528	0.1159	-0.0617	-0.0766	0.1807	0.07	0.2151	-7.7	-3.3324	17.594
8	0.0427	0.4988	-0.3481	5.9574	-3.5101	6.1169	-0.0269	0.0126	0.0126	-0.0595	0.0962	0.1852	0.5105	-0.4782	-0.0693	0.1443	-0.0402	0.0558	0.1596	-0.0055	0.062	-16.6053	-9.5072	17.7995
9	1.5094	-2.1096	3.418	10.2042	-5.1416	10.2158	0.1605	0.2339	-0.0284	-0.5549	-0.1345	0.1735	0.5722	-0.3761	-0.026	0.0497	-0.0536	0.0042	0.3691	-0.0233	0.0348	-17.9461	-1.0458	1.805
10	3.5375	-1.3103	0.861	2.0776	-3.8875	8.2965	-0.1992	0.2699	-0.0979	0.005	0.0358	-0.0772	-0.0317	-0.3014	0.1634	0.2397	0.0325	0.1128	0.1626	-0.0278	0.1051	-12.1139	-0.0683	-6.049
11	5.0551	-0.1503	-4.9523	6.9976	-2.8	6.0986	-0.0797	0.1902	-0.1693	-0.0542	-0.0466	0.049	0.1108	-0.1589	0.1262	0.091	0.0131	0.0181	0.1124	-0.0301	0.1429	-11.3122	-10.2786	-0.0011
12	3.8111	0.1023	0.182	0.7332	-2.3865	8.2303	0.0306	0.1775	-0.1176	-0.0102	-0.001	-0.0707	0.1754	-0.0271	-0.0296	0.2017	-0.0036	0.009	0.1022	-0.015	0.2536	-10.8674	-19.5711	10.6974

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	A	43 - 51
2	X-RAY DIFFRACTION	2	A	52 - 59
3	X-RAY DIFFRACTION	3	A	60 - 70
4	X-RAY DIFFRACTION	4	A	71 - 86
5	X-RAY DIFFRACTION	5	A	87 - 98
6	X-RAY DIFFRACTION	6	A	99 - 109
7	X-RAY DIFFRACTION	7	A	110 - 117
8	X-RAY DIFFRACTION	8	A	118 - 127
9	X-RAY DIFFRACTION	9	A	128 - 142
10	X-RAY DIFFRACTION	10	A	143 - 150
11	X-RAY DIFFRACTION	11	A	151 - 158
12	X-RAY DIFFRACTION	12	A	159 - 168

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