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- PDB-6u72: BRD4-BD1 in complex with the cyclic peptide 3.1_2_AcK5toA -

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Open data


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Basic information

Entry
Database: PDB / ID: 6u72
TitleBRD4-BD1 in complex with the cyclic peptide 3.1_2_AcK5toA
Components
  • 3.1_2_AcK5toA
  • Bromodomain-containing protein 4
KeywordsTRANSCRIPTION/INHIBITOR / BET / bromodomain / macrocyclic peptide / BRD4 / inhibitor / RaPID / TRANSCRIPTION-INHIBITOR complex
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 ...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 / 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 / chromatin / 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
Similarity search - Function
Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / NET domain superfamily / NET domain profile. / Brdt, bromodomain, repeat II / Brdt, bromodomain, repeat I / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. ...Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / NET domain superfamily / NET domain profile. / Brdt, bromodomain, repeat II / Brdt, bromodomain, repeat I / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily
Similarity search - Domain/homology
AMINO GROUP / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsPatel, K. / Walshe, J.L. / Walport, L.J. / Mackay, J.P. / Mouradian, K.S.
Funding support Australia, 1items
OrganizationGrant numberCountry
National Health and Medical Research Council (NHMRC, Australia)APP1161623 Australia
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2020
Title: Cyclic peptides can engage a single binding pocket through highly divergent modes.
Authors: Patel, K. / Walport, L.J. / Walshe, J.L. / Solomon, P.D. / Low, J.K.K. / Tran, D.H. / Mouradian, K.S. / Silva, A.P.G. / Wilkinson-White, L. / Norman, A. / Franck, C. / Matthews, J.M. / Guss, ...Authors: Patel, K. / Walport, L.J. / Walshe, J.L. / Solomon, P.D. / Low, J.K.K. / Tran, D.H. / Mouradian, K.S. / Silva, A.P.G. / Wilkinson-White, L. / Norman, A. / Franck, C. / Matthews, J.M. / Guss, J.M. / Payne, R.J. / Passioura, T. / Suga, H. / Mackay, J.P.
History
DepositionAug 31, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 19, 2020Provider: repository / Type: Initial release
Revision 1.1Mar 3, 2021Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Oct 11, 2023Group: Advisory / Data collection ...Advisory / Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_unobs_or_zero_occ_atoms
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.3Nov 15, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Bromodomain-containing protein 4
B: Bromodomain-containing protein 4
C: 3.1_2_AcK5toA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,2364
Polymers36,2203
Non-polymers161
Water1,13563
1
B: Bromodomain-containing protein 4
C: 3.1_2_AcK5toA
hetero molecules

A: Bromodomain-containing protein 4


Theoretical massNumber of molelcules
Total (without water)36,2364
Polymers36,2203
Non-polymers161
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_655x+1,y,z1
Buried area2740 Å2
ΔGint-19 kcal/mol
Surface area13760 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.213, 49.048, 59.146
Angle α, β, γ (deg.)90.000, 103.874, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

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Components

#1: Protein Bromodomain-containing protein 4 / Protein HUNK1


Mass: 17200.648 Da / Num. of mol.: 2
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: Protein/peptide 3.1_2_AcK5toA


Mass: 1819.134 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)
#3: Chemical ChemComp-NH2 / AMINO GROUP


Mass: 16.023 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: NH2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 63 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

CrystalDensity Matthews: 2.77 Å3/Da / Density % sol: 55.65 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop
Details: 5% v/v (+/-)-2-Methyl-2,4-pentanediol, 0.1 M HEPES pH 7.5, 10% w/v Polyethylene glycol 10,000

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9537 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Aug 24, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 2.3→46.2 Å / Num. obs: 14604 / % possible obs: 99.9 % / Redundancy: 6.7 % / Biso Wilson estimate: 41.49 Å2 / CC1/2: 0.995 / Net I/σ(I): 7.8
Reflection shellResolution: 2.3→2.36 Å / Num. unique obs: 1431 / CC1/2: 0.942

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Processing

Software
NameVersionClassification
PHENIX1.14_3260refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4LYI

4lyi


Resolution: 2.3→46.2 Å / SU ML: 0.2986 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 31.3363
RfactorNum. reflection% reflection
Rfree0.2661 714 4.91 %
Rwork0.2093 --
obs0.212 14555 99.63 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 59.63 Å2
Refinement stepCycle: LAST / Resolution: 2.3→46.2 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2077 0 1 63 2141
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00332135
X-RAY DIFFRACTIONf_angle_d0.53332896
X-RAY DIFFRACTIONf_chiral_restr0.0364310
X-RAY DIFFRACTIONf_plane_restr0.0033367
X-RAY DIFFRACTIONf_dihedral_angle_d8.23731292
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.3-2.480.37441590.29062723X-RAY DIFFRACTION99.55
2.48-2.730.37061500.27972741X-RAY DIFFRACTION99.42
2.73-3.120.2681140.24922774X-RAY DIFFRACTION99.79
3.12-3.930.24471420.20662766X-RAY DIFFRACTION99.69
3.93-46.20.23271490.16762837X-RAY DIFFRACTION99.7
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°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)
12.21401166501-0.3623015064392.26186186754.8002525724-3.609341742694.498706626211.113270194220.648863458168-1.119449908890.3526611658320.5702617229930.7155256237190.611809361889-1.11256721346-0.741746220940.3059033130540.04166031943740.01763450166340.608697062849-0.2448097205370.58066568958733.12106210081.8349747676926.3543581424
20.565585226976-0.0719234894835-0.2328385407151.38109437373-0.7450037766240.527471218490.3360925624921.02337276845-0.610286862411-0.201907056416-0.1520298227470.217002285560.2371533274390.4026371815050.2523893612410.3148494968510.35392136056-0.002658941092641.20350844412-0.8169600988710.53079976558530.0262874713-3.3710532239411.6632587941
32.30601655902-1.989364687570.6371142715392.97005741189-3.469219022386.870409524671.041921851510.905833334127-0.925603531521-0.00551401733678-0.326788259974-0.5599032227750.0384296825997-0.607782531653-0.575231449670.9925302410910.152512769653-0.1613457304481.3451709732-0.3236600980960.80680738372723.27727517711.792081213857.91946947422
45.804178228992.275603950285.260026427473.447737786261.634621131224.901610440720.1564273989571.283082637050.661199136436-0.367726619373-0.8756269794130.99363297683-0.352708586389-0.5198248537430.8030540954320.5525661010730.2957357420470.02580974691040.845808702757-0.08327606385990.510361625435.87829053516.1300244651516.3242398147
54.53069611696-5.958718565745.98818159917.85110309016-7.88410774977.92072710752-1.39691109801-0.7930215391750.4131457154781.663051723530.538315207817-0.176795751850.6237108704660.7654147888830.3666413165380.5671249661080.08536560997370.2391796780240.57955721051-0.10972188270.3040367103248.93318240044.9288301222226.2572134777
63.002568702320.1202581083442.87919693461.45774465193-0.6147650957313.200852566280.4916874840251.113899427880.409162115311-0.539192857934-0.3712167956750.0792248028132-1.127769698860.202273627963-0.2421615945680.6486400166160.2892310455240.1140674522760.7999437417530.03399840383670.34885575264244.59657890474.4464365052410.0954884462
74.50714161991-3.23978721266-0.004334572513959.49663827822-1.951386808177.306892480830.023100725673-0.467708634698-0.9933211024140.319001383803-0.2450848026790.3547848131690.3237636404130.420974204090.1729230968410.382468645896-0.03220377081640.1249629333020.4130706228180.08163646878620.27298033410155.1050401117-11.232640175424.4696033005
87.687965964310.1364340830421.44198756520.7059035298040.9231284322831.434390910480.508283709601-0.3949515355360.204591919814-0.7310130509540.227612586619-0.42060910502-0.509544166969-0.218315978828-0.1268849517670.6755320367790.04524675041220.2609619617310.453732134058-0.01632330408310.3099730994295.1869715739-9.579914023723.86941035282
91.10722463405-1.736498860180.305122949442.852751629930.1595337931484.09272472915-0.1834430450770.2285919388850.10838056365-0.679426775383-0.370127335576-0.556266434128-0.1627756423320.7781766739650.2890006437560.817030626134-0.1247245666110.1765002897240.3093524005280.08029723717240.5167820099448.1874640280111.3451072556-0.876801416951
106.50513430877-1.02062385451.310918377976.11608983681-0.7609630023962.02920942415-0.111714067521-0.472316523556-0.3880684724810.0993354066297-0.225557978983-0.6078399008960.492047512910.9935467215240.2490704683740.432227922626-0.0003622224975790.04818881721640.480854853130.0748180526260.35367365222114.96738203184.089768228416.1543909563
112.883614835171.604958580833.594396226625.267163857311.022404350685.004755984820.291470404822-0.109614252151-0.7011264190690.578505437095-0.0360748447511-0.09941214729840.8924240452550.371290972534-0.1915719659880.72921091690.1939668345540.08053455873810.3768365159250.04957053281980.369291965437.76093466094-12.303565272415.2526856327
123.529878189551.950010295331.451041966246.090258438770.4074978777773.90026558479-0.06313862254070.084435513004-0.375893918240.0379138267989-0.0415333743533-0.6101614528580.3452335839680.6728347728790.01157672676540.4095315338060.1052694658760.1315100858140.350847353978-0.02558214580290.3088084014124.87790015228-3.014361545338.29084551563
138.46473330917-4.352379468595.823130474793.13901207706-1.318204962117.09855054159-0.5990399163710.8566640391960.680178363538-0.630751323288-0.208591340421-0.4011430360560.3259727662190.2996382440930.8035448304160.572785598981-0.07257409613210.1745008430490.3301153730250.0134690339690.4416622097545.183319885648.33673428022-1.95130255556
142.553891697153.00811554576-2.135275616545.50863854697-3.567924988419.52586991798-0.0643441590409-0.0640887628315-0.0325252580727-0.23976422230.297682345455-0.153430333871-0.1047385383670.377149071417-0.3228287282620.3134977718830.05171016705780.08659466516230.183923833727-0.01033397326820.2384474724651.101024230723.657463738412.7632056442
159.261617905054.334921866362.125782953936.730810701854.953845823783.826841504090.676609380906-2.82441316445-0.5189440901471.22513234435-0.1331211416390.2551611504120.3047783749230.511413978032-0.4751113626530.4839280754790.02677676500720.06682805256740.5325686071940.1055584691960.3712138616381.06345538511-4.0286689353427.397034336
166.322319368142.43762257415-1.095807846064.27253926734-5.215323625717.137691310480.49614187757-0.4655523637280.5978067869791.300427837270.05484724328990.746841715258-1.327536349690.767265618187-0.3801952726130.547273710478-0.04432025499560.07847875044410.335576767048-0.03752187648740.3057441601337.611685259858.721659476920.2345404512
172.76725569778-3.85984063894.159860494735.38641382858-5.80846444226.25786571993-1.427265807111.410352237990.0968386894858-0.926174848355-0.657762301801-1.90642284896-1.614030244950.5661301541881.963418458150.877334343374-0.1456310870220.01117517603220.6758163634290.1051622487310.6022133274037.4072768098222.17536980533.60206336262
184.945473402810.194740771079-5.252958129367.635129871324.755539402838.82420491281-0.05623554028212.85287540881-0.0686392254937-0.0216429788649-0.1492853965360.5582236654640.379060807009-0.0093214696420.1091533480161.126857062490.46580919164-0.1852005118591.79303268538-0.3181428839550.763233042330.70193421450.8807159172870.0285680060406
190.569650919471-0.3743247537190.181349066372.03347571409-0.2243426353426.411782864040.6017444024870.3345058670260.013476033135-0.590542381875-0.2426862104090.1808295638890.619200100849-0.5764968394790.2859120400770.7800336598550.580816536913-0.5655313056871.81510272833-0.6879311315280.27073353045838.6422871246-3.988475700826.16978872537
203.892620998941.58649240832-2.578394414930.753064865714-1.320206580842.271768557641.06237129571.53939133455-0.699703005672-0.746280074615-0.9306337469950.07052294355240.206016770692-0.620685927262-0.07310563832630.9491629353890.264897717435-0.02352626217780.436413250159-0.1178359545780.4285858094445.1111856408-5.6167170313913.9674138177
219.31070608294-3.05142507848-4.731378514763.188507603233.217811187783.81391058696-0.0334840334589-0.639550601839-1.02806240229-0.185406311537-0.6242022691170.753028737168-0.0876538969891-0.3268085351360.8798976585820.605270016316-0.01211452827960.03018359752120.3718359507050.05864021216260.60733806403237.3846549465-6.8181138629627.6997123904
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'B' and (resid 97 through 106 )
2X-RAY DIFFRACTION2chain 'B' and (resid 107 through 114 )
3X-RAY DIFFRACTION3chain 'B' and (resid 115 through 121 )
4X-RAY DIFFRACTION4chain 'B' and (resid 122 through 139 )
5X-RAY DIFFRACTION5chain 'B' and (resid 140 through 144 )
6X-RAY DIFFRACTION6chain 'B' and (resid 145 through 164 )
7X-RAY DIFFRACTION7chain 'C' and (resid 1 through 14 )
8X-RAY DIFFRACTION8chain 'A' and (resid 42 through 51 )
9X-RAY DIFFRACTION9chain 'A' and (resid 52 through 68 )
10X-RAY DIFFRACTION10chain 'A' and (resid 69 through 83 )
11X-RAY DIFFRACTION11chain 'A' and (resid 84 through 96 )
12X-RAY DIFFRACTION12chain 'A' and (resid 97 through 115 )
13X-RAY DIFFRACTION13chain 'A' and (resid 116 through 121 )
14X-RAY DIFFRACTION14chain 'A' and (resid 122 through 139 )
15X-RAY DIFFRACTION15chain 'A' and (resid 140 through 144 )
16X-RAY DIFFRACTION16chain 'A' and (resid 145 through 163 )
17X-RAY DIFFRACTION17chain 'A' and (resid 164 through 168 )
18X-RAY DIFFRACTION18chain 'B' and (resid 60 through 68 )
19X-RAY DIFFRACTION19chain 'B' and (resid 69 through 75 )
20X-RAY DIFFRACTION20chain 'B' and (resid 76 through 83 )
21X-RAY DIFFRACTION21chain 'B' and (resid 84 through 96 )

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