PDB-7npz: C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH (R)-N5-cyclopropyl-N3-m...

ID or keywords:

Entry

Database: PDB / ID: 7npz

Title

C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH (R)-N5-cyclopropyl-N3-methyl-2-oxo-1-(1-phenylethyl)-1,2-dihydropyridine-3,5-dicarboxamide

Components

Bromodomain-containing protein 2

Keywords

NUCLEAR PROTEIN / INHIBITOR / HISTONE / EPIGENETIC READER / BROMODOMAIN / BRD2 / BROMODOMAIN CONTAINING PROTEIN 2 / ANTAGONIST

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 / nuclear speck ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

FOURIER SYNTHESIS / Resolution: 1.28 Å

Authors

Chung, C.

Citation

Journal: J.Med.Chem. / Year: 2021
Title: Identification of a Series of N -Methylpyridine-2-carboxamides as Potent and Selective Inhibitors of the Second Bromodomain (BD2) of the Bromo and Extra Terminal Domain (BET) Proteins.
Authors: Harrison, L.A. / Atkinson, S.J. / Bassil, A. / Chung, C.W. / Grandi, P. / Gray, J.R.J. / Levernier, E. / Lewis, A. / Lugo, D. / Messenger, C. / Michon, A.M. / Mitchell, D.J. / Preston, A. / ...

History

Deposition	Feb 28, 2021	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Jul 21, 2021	Provider: repository / Type: Initial release
Revision 1.1	Aug 25, 2021	Group: Database references / Category: citation / database_2 Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2	May 1, 2024	Group: Data collection / Derived calculations / Refinement description Category: atom_type / chem_comp_atom ...atom_type / chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model Item: _atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	7npz.cif.gz	62.8 KB	Display	PDBx/mmCIF format
PDB format	pdb7npz.ent.gz		Display	PDB format
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Validation report

Summary document	7npz_validation.pdf.gz	753.3 KB	Display	wwPDB validaton report
Full document	7npz_full_validation.pdf.gz	753.3 KB	Display
Data in XML	7npz_validation.xml.gz	9.2 KB	Display
Data in CIF	7npz_validation.cif.gz	13.2 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/np/7npz ftp://data.pdbj.org/pub/pdb/validation_reports/np/7npz	HTTPS FTP

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Related structure data

Related structure data	7npyC 7nq0C 7nq1C 7nq2C 7nq3C C: citing same article (ref.)
Similar structure data	7jx7-d 5dw1-1 7nq9-d 5dw1-4 7nq8-d 6e6j-5 7npy-d 5dw1-2 5o3f-d 5uer-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	#7 - Jul 2000 Nucleosome similarity (1) #122 - Feb 2010 Enhanceosome similarity (1)

Deposited unit

AAA: Bromodomain-containing protein 2

hetero molecules

14 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software
Evidence: gel filtration

Unit cell

Length a, b, c (Å)	71.860, 52.310, 31.970
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	18
Space group name H-M	P2₁2₁2

Components on special symmetry positions

ID	Model	Components
1	1	AAA-731- HOH

#1: Protein	Bromodomain-containing protein 2 / O27.1.1 / Really interesting new gene 3 protein Mass: 13432.462 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRD2, KIAA9001, RING3 / Production host: Escherichia coli (E. coli) / References: UniProt: P25440
#2: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C₂H₆O₂
#3: Chemical	ChemComp-ULH / ~{N}5-cyclopropyl-~{N}3-methyl-2-oxidanylidene-1-[(1~{R})-1-phenylethyl]pyridine-3,5-dicarboxamide Mass: 339.388 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₉H₂₁N₃O₃ / Feature type: SUBJECT OF INVESTIGATION
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 217 / 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: 2.24 Å³/Da / Density % sol: 45.01 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion / pH: 6.5 / Details: 30% PEG 300, 0.1M MES buffer pH6.5

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97625 Å
Detector	Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 6, 2015
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97625 Å / Relative weight: 1
Reflection	Resolution: 1.28→35.93 Å / Num. obs: 30641 / % possible obs: 96.8 % / Redundancy: 4.4 % / CC_1/2: 0.998 / Net I/σ(I): 15.1
Reflection shell	Resolution: 1.28→1.31 Å / Redundancy: 2.6 % / Mean I/σ(I) obs: 1.6 / Num. unique obs: 1914 / CC_1/2: 0.492 / % possible all: 84.8

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0258	refinement
XDS		data reduction
Aimless		data scaling

Refinement

Method to determine structure:

FOURIER SYNTHESIS
Starting model: in house

Resolution: 1.28→35.93 Å / Cor.coef. F_o:F_c: 0.971 / Cor.coef. F_o:F_c free: 0.963 / SU B: 1.734 / SU ML: 0.036 / Cross valid method: FREE R-VALUE / ESU R: 0.051 / ESU R Free: 0.052
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.1933	1542	5.04 %
R_work	0.1736	29052	-
all	0.175	-	-
obs	-	30594	96.141 %

Solvent computation

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

Displacement parameters

B_iso mean: 19.46 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.005 Å²	-0 Å²	0 Å²
2-	-	0.003 Å²	-0 Å²
3-	-	-	-0.007 Å²

Refinement step

Cycle: LAST / Resolution: 1.28→35.93 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	914	0	37	217	1168

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.005	0.013	993
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.017	915
X-RAY DIFFRACTION	r_angle_refined_deg	1.202	1.658	1334
X-RAY DIFFRACTION	r_angle_other_deg	1.36	1.624	2122
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	4.916	5	113
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	29.727	21.607	56
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	11.576	15	171
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	19.301	15	7
X-RAY DIFFRACTION	r_chiral_restr	0.066	0.2	116
X-RAY DIFFRACTION	r_gen_planes_refined	0.006	0.02	1095
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	222
X-RAY DIFFRACTION	r_nbd_refined	0.206	0.2	209
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.164	0.2	794
X-RAY DIFFRACTION	r_nbtor_refined	0.174	0.2	487
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.082	0.2	356
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.082	0.2	136
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.121	0.2	10
X-RAY DIFFRACTION	r_nbd_other	0.162	0.2	55
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.052	0.2	24
X-RAY DIFFRACTION	r_mcbond_it	0.845	1.998	452
X-RAY DIFFRACTION	r_mcbond_other	0.835	1.989	451
X-RAY DIFFRACTION	r_mcangle_it	1.434	4.45	565
X-RAY DIFFRACTION	r_mcangle_other	1.436	4.464	566
X-RAY DIFFRACTION	r_scbond_it	1.296	2.305	541
X-RAY DIFFRACTION	r_scbond_other	1.294	2.305	542
X-RAY DIFFRACTION	r_scangle_it	2.157	4.98	766
X-RAY DIFFRACTION	r_scangle_other	2.155	4.981	767
X-RAY DIFFRACTION	r_lrange_it	5.097	20.517	1245
X-RAY DIFFRACTION	r_lrange_other	5.095	20.524	1246

LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 20

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	R_factor all	Num. reflection all	Fsc free	Fsc work	% reflection obs (%)	WR_factor R_work
1.28-1.313	0.338	95	0.309	1812	0.31	2291	0.781	0.77	83.2388	0.289
1.313-1.349	0.275	111	0.281	1982	0.28	2264	0.842	0.827	92.447	0.259
1.349-1.388	0.252	95	0.246	2029	0.247	2198	0.861	0.88	96.6333	0.219
1.388-1.431	0.253	100	0.22	2003	0.221	2116	0.912	0.91	99.3856	0.198
1.431-1.478	0.199	105	0.212	1963	0.211	2082	0.937	0.923	99.3276	0.187
1.478-1.53	0.218	117	0.194	1882	0.196	2018	0.935	0.941	99.0585	0.171
1.53-1.587	0.206	76	0.178	1841	0.179	1930	0.941	0.95	99.3264	0.158
1.587-1.652	0.217	92	0.176	1751	0.178	1860	0.946	0.954	99.086	0.155
1.652-1.725	0.152	86	0.168	1687	0.167	1778	0.966	0.962	99.7188	0.151
1.725-1.809	0.192	82	0.168	1636	0.169	1741	0.955	0.962	98.6789	0.153
1.809-1.907	0.193	88	0.173	1527	0.174	1638	0.958	0.958	98.5958	0.163
1.907-2.022	0.186	104	0.167	1429	0.168	1563	0.962	0.962	98.0806	0.164
2.022-2.161	0.162	67	0.156	1358	0.156	1461	0.966	0.965	97.5359	0.159
2.161-2.334	0.181	63	0.155	1282	0.157	1381	0.961	0.966	97.3932	0.162
2.334-2.555	0.185	69	0.157	1162	0.159	1280	0.956	0.967	96.1719	0.17
2.555-2.855	0.208	51	0.165	1047	0.167	1147	0.952	0.962	95.728	0.186
2.855-3.293	0.159	48	0.161	920	0.161	1038	0.962	0.957	93.2563	0.185
3.293-4.025	0.173	41	0.148	773	0.149	893	0.957	0.969	91.1534	0.178
4.025-5.657	0.225	35	0.162	605	0.165	708	0.961	0.966	90.3955	0.201
5.657-35.93	0.172	17	0.211	363	0.209	434	0.964	0.959	87.5576	0.268

Refinement TLS params.

Method: refined / Origin x: 32.9496 Å / Origin y: 10.2421 Å / Origin z: 1.0088 Å

	11	12	13	21	22	23	31	32	33
T	0.0258 Å²	0.005 Å²	0.0029 Å²	-	0.0149 Å²	-0.0007 Å²	-	-	0.0059 Å²
L	0.5399 °²	0.1033 °²	0.1008 °²	-	0.3061 °²	0.0465 °²	-	-	0.0737 °²
S	0.0229 Å °	0.0237 Å °	-0.0169 Å °	0.0173 Å °	-0.0128 Å °	-0.0064 Å °	-0.0293 Å °	-0.0087 Å °	-0.0101 Å °

Refinement TLS group

Selection: ALL

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