SASDB96: Compound 1:BRD4 (1:1) (Bromodomain-containing protein 4, BRD4)

Basic information

• Entry: Database: SASBDB / ID: SASDB96

Sample

Compound 1:BRD4 (1:1)

• Bromodomain-containing protein 4 (protein), BRD4, Homo sapiens

Function / homology

Function:

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 / transcription coregulator activity / lysine-acetylated histone binding / p53 binding / chromosome / regulation of inflammatory response / positive regulation of canonical NF-kappaB signal transduction / Potential therapeutics for SARS / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / enzyme binding / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus

Domain/homology:

Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat I / Brdt, bromodomain, repeat II / NET domain superfamily / NET domain profile. / : / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily

Component:

Bromodomain-containing protein 4

• Biological species: Homo sapiens (human)
• Citation: Date: 2016 Oct 24; Title: Potent and selective bivalent inhibitors of BET bromodomains; Authors: Waring M / Chen H / Rabow A / Walker G / Bobby R / Boiko S / Bradbury R / Callis R / Clark E / Dale I / Daniels D / Dulak A / Flavell L / Holdgate G / Jowitt T / Kikhney A / McAlister M / Méndez J / Ogg D / Patel J / Petteruti P / Robb G / Robers M / Saif S / Stratton N / Svergun D / Wang W / Whittaker D / Wilson D

Contact author

• Al Kikhney (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

Models

• Model #587: ; Type: dummy / Software: DAMMIF (r4311) / Radius of dummy atoms: 5.80 A / Chi-square value: 9.560464; Search similar-shape structures of this assembly by Omokage search (details)
• Model #769: ; Type: mix / Software: RANCH / Radius of dummy atoms: 1.90 A / Chi-square value: 12.837889; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Compound 1:BRD4 (1:1) / Specimen concentration: 1.00-10.00
• Buffer: Name: 20mM Hepes, 100mM NaCl, 1mM Tris(2-carboxyethyl)phosphine hydrochloride; pH: 7.4

Entity #394

Name: BRD4 / Type: protein / Description: Bromodomain-containing protein 4 / Formula weight: 55.836 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: O60885
Sequence:

MAHHHHHHSS GVDLGTENLY FQSMMSAESG PGTRLRNLPV MGDGLETSQM STTQAQAQPQ PANAASMNPP PPETSNPNKP KRQTNQLQYL LRVVLKTLWK HQFAWPFQQP VDAVKLNLPD YYKIIKTPMD MGTIKKRLEN NYYWNAQECI QDFNTMFTNC YIYNKPGDDI VLMAEALEKL FLQKINELPT EETEIMIVQA KGRGRGRKET GTAKPGVSTV PNTTQASTPP QTQTPQPNPP PVQATPHPFP AVTPDLIVQT PVMTVVPPQP LQTPPPVPPQ PQPPPAPAPQ PVQSHPPIIA ATPQPVKTKK GVKRKADTTT PTTIDPIHEP PSLPPEPKTT KLGQRRESSR PVKPPKKDVP DSQQHPAPEK SSKVSEQLKC CSGILKEMFA KKHAAYAWPF YKPVDVEALG LHDYCDIIKH PMDMSTIKSK LEAREYRDAQ EFGADVRLMF SNCYKYNPPD HEVVAMARKL QDVFEMRFAK MPDEPEEPVV AVSSPAVPPP T

Experimental information

• Beam: Instrument name: ESRF BM29 / City: Grenoble / 国: France / Type of source: X-ray synchrotron / Wavelength: 0.0992 Å / Dist. spec. to detc.: 2.87 mm
• Detector: Name: Pilatus 1M

Scan

Title: Compound 1:BRD4 (1:1) / Measurement date: Sep 12, 2014 / Exposure time: 0.2 sec. / Number of frames: 50 / Unit: 1/nm /

	Min	Max
Q	0.0363	4.9693

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 249 /

	Min	Max
Q	0.1074	1.281
P(R) point	16	264
R	0	27.5

Result

Type of curve: extrapolated
Comments: A pool of 10000 models comprising two rigid bromodomains (residues 42-168, PDB ID: 2oss and 349-458, PDB ID: 2yem) connected by a flexible linker, N-terminal tag and flexible N- and C-termini were generated by the program RANCH (EOM). The scattering from each model from the pool was calculated with the program CRYSOL. For the 100 models best fitting the experimental scattering the histograms of the distances between the centres of the two bromodomains were computed; the average distance was 13±2 nm, the average Rg was 6.6±0.7 nm.

	Experimental	Standard
MW	37.2 kDa	37.2 kDa

	P(R)	Guinier	Guinier error
Forward scattering, I0	48.37	46.3549	-
Radius of gyration, Rg	7.1 nm	6.223 nm	0.659

	Min	Max
D	-	27.5
Guinier point	17	35