PDB-8q34: Crystal structure of the first bromodomain of human BRD4 in compl...

ID or keywords:

Entry

Database: PDB / ID: 8q34

Title

Crystal structure of the first bromodomain of human BRD4 in complex with the ligand ZZ001229a

Components

Bromodomain-containing protein 4

Keywords

GENE REGULATION / Ligand Complex / Bromodomain / Covalent

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 / RNA polymerase II CTD heptapeptide repeat kinase activity / histone reader 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 /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.48 Å

Authors

MacLean, E.M. / Gao, Q. / Williams, E. / Balcomb, B.H. / von Delft, F. / Bajusz, D. / Keeley, A. / Abranyi-Balogh, P. / Koekemoer, L. / Keseru, G.M.

Funding support

1items

Citation

Journal: Commun Chem / Year: 2024
Title: Mapping protein binding sites by photoreactive fragment pharmacophores.
Authors: Abranyi-Balogh, P. / Bajusz, D. / Orgovan, Z. / Keeley, A.B. / Petri, L. / Peczka, N. / Szalai, T.V. / Palfy, G. / Gadanecz, M. / Grant, E.K. / Imre, T. / Takacs, T. / Randelovic, I. / ...

History

Deposition	Aug 3, 2023	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Feb 7, 2024	Provider: repository / Type: Initial release
Revision 1.1	Aug 14, 2024	Group: Database references / Category: citation / citation_author

Structure viewer	Molecule: MolmilJmol/JSmol

-
Download

PDBx/mmCIF format	8q34.cif.gz	236.7 KB	Display	PDBx/mmCIF format
PDB format	pdb8q34.ent.gz	186 KB	Display	PDB format
PDBx/mmJSON format	8q34.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

-
Validation report

Summary document	8q34_validation.pdf.gz	1.4 MB	Display	wwPDB validaton report
Full document	8q34_full_validation.pdf.gz	1.4 MB	Display
Data in XML	8q34_validation.xml.gz	29.4 KB	Display
Data in CIF	8q34_validation.cif.gz	44.2 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/q3/8q34 ftp://data.pdbj.org/pub/pdb/validation_reports/q3/8q34	HTTPS FTP

-
Related structure data

Similar structure data	Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

-
Links

PDB pages	PDBj / wwPDB / NCBI

Deposited unit

A: Bromodomain-containing protein 4

B: Bromodomain-containing protein 4

C: Bromodomain-containing protein 4

D: Bromodomain-containing protein 4

hetero molecules

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

1

A: Bromodomain-containing protein 4

hetero molecules

defined by author
Evidence: gel filtration
15.8 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Bromodomain-containing protein 4

hetero molecules

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

3

C: Bromodomain-containing protein 4

hetero molecules

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

4

D: Bromodomain-containing protein 4

hetero molecules

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

Unit cell

Length a, b, c (Å)	37.239, 44.093, 78.479
Angle α, β, γ (deg.)	90.033, 90.000, 90.026
Int Tables number	1
Space group name H-M	P1

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	A
2	1	A
3	2	A
4	2	A
5	3	A
6	3	A
7	4	A
8	4	A
9	5	A
10	5	A
11	6	A
12	6	A

NCS domain segments:

Auth asym-ID: A / Label asym-ID: A

Dom-ID	Component-ID	Ens-ID	Beg auth comp-ID	Beg label comp-ID	End auth comp-ID	End label comp-ID	Auth seq-ID	Label seq-ID
1	1	1	SER	SER	GLU	GLU	42 - 168	1 - 127
2	1	1	SER	SER	GLU	GLU	42 - 168	1 - 127
3	2	2	MET	MET	GLU	GLU	43 - 167	2 - 126
4	2	2	MET	MET	GLU	GLU	43 - 167	2 - 126
5	3	3	SER	SER	THR	THR	42 - 166	1 - 125
6	3	3	SER	SER	THR	THR	42 - 166	1 - 125
7	4	4	MET	MET	GLU	GLU	43 - 167	2 - 126
8	4	4	MET	MET	GLU	GLU	43 - 167	2 - 126
9	5	5	SER	SER	THR	THR	42 - 166	1 - 125
10	5	5	SER	SER	THR	THR	42 - 166	1 - 125
11	6	6	MET	MET	THR	THR	43 - 166	2 - 125
12	6	6	MET	MET	THR	THR	43 - 166	2 - 125

NCS ensembles :

ID	Details
1	Local NCS retraints between domains: 1 2
2	Local NCS retraints between domains: 3 4
3	Local NCS retraints between domains: 5 6
4	Local NCS retraints between domains: 7 8
5	Local NCS retraints between domains: 9 10
6	Local NCS retraints between domains: 11 12

#1: Protein	Bromodomain-containing protein 4 / Protein HUNK1 Mass: 15442.756 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: O60885
#2: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₂H₆O₂
#3: Chemical	ChemComp-IX4 / ~{N}-(1~{H}-imidazo[4,5-b]pyridin-2-ylmethyl)-3-(3-methyl-1,2-diazirin-3-yl)propanamide Mass: 258.279 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₁₂H₁₄N₆O / Feature type: SUBJECT OF INVESTIGATION
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 804 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y

-
Experiment

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

-
Sample preparation

Crystal	Density Matthews: 2.09 Å³/Da / Density % sol: 41.04 %
Crystal grow	Temperature: 277.15 K / Method: vapor diffusion, sitting drop Details: 20% PEG6000 -- 10% ethylene glycol -- 0.1M HEPES pH 7.0 -- 0.2M sodium chloride

-
Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.9763 Å
Detector	Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 19, 2022
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9763 Å / Relative weight: 1
Reflection	Resolution: 1.48→78.479 Å / Num. obs: 75591 / % possible obs: 90.9 % / Redundancy: 3.4 % / CC_1/2: 0.994 / Net I/σ(I): 5.7
Reflection shell	Resolution: 1.48→1.506 Å / Num. unique obs: 2090 / CC_1/2: 0.394 / % possible all: 51.3

-
Processing

Software

Name	Version	Classification
REFMAC	5.8.0419	refinement
autoPROC		data reduction
autoPROC		data scaling
REFMAC		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.48→78.479 Å / Cor.coef. F_o:F_c: 0.962 / Cor.coef. F_o:F_c free: 0.939 / WR_factor R_free: 0.203 / WR_factor R_work: 0.172 / SU B: 2.222 / SU ML: 0.078 / Average fsc free: 0.9603 / Average fsc work: 0.968 / Cross valid method: FREE R-VALUE / ESU R: 0.091 / ESU R Free: 0.09
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2164	3632	4.811 %
R_work	0.1836	71867	-
all	0.185	-	-
obs	-	75499	90.769 %

Solvent computation

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

Displacement parameters

B_iso mean: 14.278 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	1.138 Å²	-0.234 Å²	-0.503 Å²
2-	-	-0.571 Å²	-0.096 Å²
3-	-	-	-0.567 Å²

Refinement step

Cycle: LAST / Resolution: 1.48→78.479 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	4224	0	92	804	5120

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.007	0.012	4495
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	4260
X-RAY DIFFRACTION	r_angle_refined_deg	2.905	1.68	6127
X-RAY DIFFRACTION	r_angle_other_deg	0.474	1.575	9854
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	5.469	5	514
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	6.601	7	20
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	14.31	10	788
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	17.294	10	217
X-RAY DIFFRACTION	r_chiral_restr	0.075	0.2	644
X-RAY DIFFRACTION	r_gen_planes_refined	0.008	0.02	5174
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	1010
X-RAY DIFFRACTION	r_nbd_refined	0.223	0.2	1038
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.192	0.2	3826
X-RAY DIFFRACTION	r_nbtor_refined	0.191	0.2	2233
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.078	0.2	2165
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.204	0.2	563
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.088	0.2	6
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.234	0.2	19
X-RAY DIFFRACTION	r_nbd_other	0.194	0.2	101
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.27	0.2	81
X-RAY DIFFRACTION	r_mcbond_it	1.393	1.397	2050
X-RAY DIFFRACTION	r_mcbond_other	1.386	1.397	2050
X-RAY DIFFRACTION	r_mcangle_it	2.185	2.497	2566
X-RAY DIFFRACTION	r_mcangle_other	2.185	2.498	2567
X-RAY DIFFRACTION	r_scbond_it	2.254	1.646	2445
X-RAY DIFFRACTION	r_scbond_other	2.254	1.645	2445
X-RAY DIFFRACTION	r_scangle_it	3.533	2.897	3549
X-RAY DIFFRACTION	r_scangle_other	3.533	2.897	3550
X-RAY DIFFRACTION	r_lrange_it	5.569	22.516	5764
X-RAY DIFFRACTION	r_lrange_other	5.319	18.051	5467
X-RAY DIFFRACTION	r_ncsr_local_group_1	0.049	0.05	4587
X-RAY DIFFRACTION	r_ncsr_local_group_2	0.062	0.05	4467
X-RAY DIFFRACTION	r_ncsr_local_group_3	0.057	0.05	4483
X-RAY DIFFRACTION	r_ncsr_local_group_4	0.052	0.05	4488
X-RAY DIFFRACTION	r_ncsr_local_group_5	0.058	0.05	4485
X-RAY DIFFRACTION	r_ncsr_local_group_6	0.064	0.05	4420

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Refine-ID	Type	Rms dev position (Å)	Weight position
1	1	A	X-RAY DIFFRACTION	Local ncs	0.04887	0.05011
1	2	A	X-RAY DIFFRACTION	Local ncs	0.04887	0.05011
2	3	A	X-RAY DIFFRACTION	Local ncs	0.06215	0.05011
2	4	A	X-RAY DIFFRACTION	Local ncs	0.06215	0.05011
3	5	A	X-RAY DIFFRACTION	Local ncs	0.05681	0.05011
3	6	A	X-RAY DIFFRACTION	Local ncs	0.05681	0.05011
4	7	A	X-RAY DIFFRACTION	Local ncs	0.05234	0.05011
4	8	A	X-RAY DIFFRACTION	Local ncs	0.05234	0.05011
5	9	A	X-RAY DIFFRACTION	Local ncs	0.05787	0.05011
5	10	A	X-RAY DIFFRACTION	Local ncs	0.05787	0.05011
6	11	A	X-RAY DIFFRACTION	Local ncs	0.06413	0.05011
6	12	A	X-RAY DIFFRACTION	Local ncs	0.06413	0.05011

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
1.48-1.519	0.317	174	0.31	3109	0.31	6171	0.925	0.927	53.2005	0.313
1.519-1.56	0.321	160	0.295	3752	0.296	5917	0.93	0.933	66.1146	0.297
1.56-1.606	0.318	243	0.282	4980	0.283	5864	0.922	0.939	89.0689	0.281
1.606-1.655	0.279	231	0.263	5104	0.264	5636	0.946	0.95	94.6593	0.258
1.655-1.709	0.254	271	0.248	5023	0.248	5553	0.957	0.957	95.3359	0.24
1.709-1.769	0.272	280	0.244	4853	0.246	5367	0.952	0.96	95.64	0.232
1.769-1.836	0.277	217	0.218	4610	0.22	5035	0.948	0.968	95.8689	0.203
1.836-1.911	0.233	211	0.199	4529	0.201	4916	0.968	0.974	96.4199	0.183
1.911-1.996	0.204	201	0.189	4392	0.19	4758	0.974	0.977	96.5322	0.174
1.996-2.093	0.196	192	0.184	4133	0.184	4480	0.973	0.98	96.5402	0.168
2.093-2.206	0.197	274	0.16	3962	0.162	4352	0.977	0.985	97.3346	0.149
2.206-2.34	0.18	223	0.151	3716	0.153	4042	0.98	0.986	97.4518	0.139
2.34-2.501	0.172	142	0.151	3606	0.152	3834	0.984	0.987	97.7569	0.141
2.501-2.701	0.269	162	0.153	3284	0.157	3531	0.954	0.986	97.5928	0.144
2.701-2.959	0.199	143	0.157	3041	0.159	3256	0.979	0.984	97.7887	0.151
2.959-3.308	0.237	127	0.168	2786	0.171	2963	0.97	0.982	98.3125	0.163
3.308-3.818	0.144	133	0.153	2440	0.153	2611	0.987	0.988	98.5446	0.153
3.818-4.674	0.198	132	0.145	2074	0.148	2233	0.969	0.986	98.7909	0.149
4.674-6.598	0.215	79	0.192	1593	0.193	1690	0.989	0.986	98.9349	0.199
6.598-78.479	0.235	37	0.178	880	0.18	946	0.978	0.985	96.9345	0.192

-
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

-
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

-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

-
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