PDB-9qw8: FKBP12 in complex with bifunctional ligand 1ad and the first brom...

ID or keywords:

Entry

Database: PDB / ID: 9qw8

Title

FKBP12 in complex with bifunctional ligand 1ad and the first bromodomain of BRD4

Components

Bromodomain-containing protein 4
Peptidyl-prolyl cis-trans isomerase FKBP1A

Keywords

ISOMERASE / Complex / Inhibitor / Bifunctional

Function / homology

Function and homology information

macrolide binding / activin receptor binding / regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion / transforming growth factor beta receptor binding / heart trabecula formation / TGFBR1 LBD Mutants in Cancer / type I transforming growth factor beta receptor binding / negative regulation of activin receptor signaling pathway / signaling receptor inhibitor activity / cytoplasmic side of membrane ...macrolide binding / activin receptor binding / regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion / transforming growth factor beta receptor binding / heart trabecula formation / TGFBR1 LBD Mutants in Cancer / type I transforming growth factor beta receptor binding / negative regulation of activin receptor signaling pathway / signaling receptor inhibitor activity / cytoplasmic side of membrane / I-SMAD binding / regulation of amyloid precursor protein catabolic process / terminal cisterna / ryanodine receptor complex / ventricular cardiac muscle tissue morphogenesis / FK506 binding / 'de novo' protein folding / histone H4K8ac reader activity / RNA polymerase II C-terminal domain binding / histone H3K27ac reader activity / negative regulation of DNA damage checkpoint / TGF-beta receptor signaling activates SMADs / P-TEFb complex binding / histone H3K9ac reader activity / histone H4 reader activity / heart morphogenesis / histone H4K5ac reader activity / histone H4K12ac reader activity / mTORC1-mediated signalling / host-mediated suppression of viral transcription / histone H4K16ac reader activity / Calcineurin activates NFAT / regulation of immune response / positive regulation of T-helper 17 cell lineage commitment / positive regulation of G2/M transition of mitotic cell cycle / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / RNA polymerase II CTD heptapeptide repeat kinase activity / supramolecular fiber organization / sarcoplasmic reticulum membrane / negative regulation of transforming growth factor beta receptor signaling pathway / condensed nuclear chromosome / T cell activation / calcium channel regulator activity / peptidylprolyl isomerase / sarcoplasmic reticulum / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / peptidyl-prolyl cis-trans isomerase activity / positive regulation of transcription elongation by RNA polymerase II / protein maturation / protein refolding / Z disc / transcription coregulator activity / p53 binding / SARS-CoV-1 activates/modulates innate immune responses / regulation of protein localization / Regulation of PD-L1(CD274) transcription / regulation of inflammatory response / protein folding / histone binding / amyloid fibril formation / Potential therapeutics for SARS / transmembrane transporter binding / positive regulation of canonical NF-kappaB signal transduction / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / chromosome / protein serine/threonine kinase activity / chromatin binding / regulation of transcription by RNA polymerase II / DNA damage response / positive regulation of DNA-templated transcription / chromatin / enzyme binding / positive regulation of transcription by RNA polymerase II / DNA-templated transcription / nucleoplasm / membrane / nucleus / cytosol / cytoplasm
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.8 Å

Authors

Meyners, C. / Hausch, F.

Funding support

Germany, 1items

Citation

Journal: Nat Commun / Year: 2026
Title: Cell type-selective targeting by heterobifunctional protein binders via in-cell enrichment.
Authors: Bulldan, A. / Zheng, M. / Meyners, C. / Purder, P.L. / Krieger, J. / Dreizler, J.K. / Geiger, T.M. / Repity, M.L. / Lein, M.H. / Quist-Lokken, I. / Tewes, N. / Smith, E.R. / Schwab, K. / ...

History

Deposition	Apr 14, 2025	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Apr 29, 2026	Provider: repository / Type: Initial release
Revision 1.1	Sep 30, 2026	Group: Database references / Category: citation / citation_author Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	9qw8.cif.gz	453.1 KB	Display	PDBx/mmCIF format
PDB format	pdb9qw8.ent.gz		Display	PDB format
PDBx/mmJSON format	9qw8.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/qw/9qw8 ftp://data.pdbj.org/pub/pdb/validation_reports/qw/9qw8	HTTPS FTP

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Related structure data

Related structure data	29qlC 9r5nC C: citing same article (ref.)
Similar structure data	Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search
Experimental dataset #1	Data reference: 10.15151/ESRF-DC-2127908021 / Data set type: diffraction image data

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#230 - Feb 2019 Initiation Factor eIF4E similarity (1) #60 - Dec 2004 Ubiquitin similarity (2) #44 - Aug 2003 Calmodulin similarity (1) #163 - Jul 2013 HIV Capsid similarity (2) #196 - Apr 2016 Lead Poisoning similarity (1) #28 - Apr 2002 Anthrax Toxin similarity (1) #245 - May 2020 Spliceosomes similarity (1) #234 - Jun 2019 MDM2 and Cancer similarity (1)

Deposited unit

A: Bromodomain-containing protein 4

B: Bromodomain-containing protein 4

D: Peptidyl-prolyl cis-trans isomerase FKBP1A

C: Peptidyl-prolyl cis-trans isomerase FKBP1A

hetero molecules

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

1

A: Bromodomain-containing protein 4

C: Peptidyl-prolyl cis-trans isomerase FKBP1A

hetero molecules

defined by author
28 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

D: Peptidyl-prolyl cis-trans isomerase FKBP1A

hetero molecules

B: Bromodomain-containing protein 4

defined by author
28 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	35.648, 35.65, 100.919
Angle α, β, γ (deg.)	86.458, 84.218, 72.475
Int Tables number	1
Space group name H-M	P1

#1: Protein	Bromodomain-containing protein 4 / Protein HUNK1 Mass: 15099.380 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 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: O60885
#2: Protein	Peptidyl-prolyl cis-trans isomerase FKBP1A / PPIase FKBP1A / 12 kDa FK506-binding protein / 12 kDa FKBP / FKBP-12 / Calstabin-1 / FK506-binding ...PPIase FKBP1A / 12 kDa FK506-binding protein / 12 kDa FKBP / FKBP-12 / Calstabin-1 / FK506-binding protein 1A / FKBP-1A / Immunophilin FKBP12 / Rotamase Mass: 11832.496 Da / Num. of mol.: 2 / Mutation: C22V Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FKBP1A, FKBP1, FKBP12 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: P62942, peptidylprolyl isomerase
#3: Chemical	ChemComp-A1JAZ / ~{N}-[2-[2-[4-[[(1~{S},5~{S},6~{R})-10-[3,5-bis(chloranyl)phenyl]sulfonyl-2-oxidanylidene-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl]methoxymethyl]-1,2,3-triazol-1-yl]ethoxy]ethyl]-2-[(9~{S})-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,7,10,12-pentaen-9-yl]ethanamide Mass: 1035.459 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₄₇H₅₀Cl₃N₁₁O₆S₂ / Feature type: SUBJECT OF INVESTIGATION
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 256 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y
Has protein modification	N

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.26 Å³/Da / Density % sol: 45.52 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: 22% PEG3350, 0.2 M NaCl, 0.1 M Tris-HCl pH 8.5

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Data collection

Diffraction

Mean temperature: 100 K / Serial crystal experiment: N

Diffraction source

Source:

SYNCHROTRON / Site:

ESRF

/ Beamline: ID23-1 / Wavelength: 0.885603 Å

Detector

Type: DECTRIS EIGER2 X CdTe 16M / Detector: PIXEL / Date: Sep 8, 2023

Radiation

Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray

Radiation wavelength

Wavelength: 0.885603 Å / Relative weight: 1

Reflection

Resolution: 1.8→100.35 Å / Num. obs: 42398 / % possible obs: 97 % / Redundancy: 3.3 % / CC_1/2: 0.977 / R_merge(I) obs: 0.078 / R_pim(I) all: 0.078 / R_rim(I) all: 0.111 / Χ²: 1.01 / Net I/σ(I): 8.4

Reflection shell

Resolution (Å)	Redundancy (%)	R_merge(I) obs	Mean I/σ(I) obs	Num. unique obs	CC_1/2	R_pim(I) all	R_rim(I) all	Χ²	% possible all
9-100.35	3.3	0.035	22	336	0.986	0.035	0.049	0.83	98.2
1.8-1.84	3.1	0.577	1.7	2462	0.563	0.577	0.816	0.96	94.6

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0430 (refmacat 0.4.100)	refinement
autoXDS		data reduction
Aimless		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.8→100.35 Å / Cor.coef. F_o:F_c: 0.936 / Cor.coef. F_o:F_c free: 0.917 / SU B: 7.302 / SU ML: 0.114 / Cross valid method: THROUGHOUT / ESU R: 0.162 / ESU R Free: 0.142
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2428	2063	4.866 %
R_work	0.2133	40333	-
all	0.215	-	-
obs	-	42396	97.02 %

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: 24.851 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.703 Å²	0.398 Å²	-0.78 Å²
2-	-	-0.27 Å²	-0.216 Å²
3-	-	-	1.11 Å²

Refinement step

Cycle: LAST / Resolution: 1.8→100.35 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3652	0	138	256	4046

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.012	0.012	3923
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	3547
X-RAY DIFFRACTION	r_angle_refined_deg	2.163	1.834	5366
X-RAY DIFFRACTION	r_angle_other_deg	0.724	1.751	8214
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.204	5	466
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	22.876	10.294	34
X-RAY DIFFRACTION	r_dihedral_angle_other_2_deg	0.646	5	2
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	14.471	10	601
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	15.179	10	169
X-RAY DIFFRACTION	r_chiral_restr	0.112	0.2	574
X-RAY DIFFRACTION	r_gen_planes_refined	0.011	0.02	4584
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	870
X-RAY DIFFRACTION	r_nbd_refined	0.224	0.2	786
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.202	0.2	3349
X-RAY DIFFRACTION	r_nbtor_refined	0.194	0.2	1959
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.093	0.2	2002
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.171	0.2	227
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.107	0.2	1
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.234	0.2	13
X-RAY DIFFRACTION	r_nbd_other	0.233	0.2	69
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.102	0.2	11
X-RAY DIFFRACTION	r_mcbond_it	1.23	1.244	1870
X-RAY DIFFRACTION	r_mcbond_other	1.228	1.244	1870
X-RAY DIFFRACTION	r_mcangle_it	1.759	2.229	2334
X-RAY DIFFRACTION	r_mcangle_other	1.759	2.229	2335
X-RAY DIFFRACTION	r_scbond_it	1.67	1.373	2053
X-RAY DIFFRACTION	r_scbond_other	1.672	1.375	2047
X-RAY DIFFRACTION	r_scangle_it	2.526	2.442	3032
X-RAY DIFFRACTION	r_scangle_other	2.526	2.442	3033
X-RAY DIFFRACTION	r_lrange_it	4.252	13.232	4468
X-RAY DIFFRACTION	r_lrange_other	4.221	13.105	4435

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
1.8-1.847	0.318	144	0.293	2945	0.294	3246	0.932	0.939	95.1633	0.289
1.847-1.897	0.275	129	0.267	2936	0.267	3147	0.939	0.949	97.3943	0.259
1.897-1.952	0.263	142	0.238	2816	0.24	3054	0.954	0.961	96.8566	0.232
1.952-2.012	0.278	135	0.227	2736	0.229	2982	0.949	0.966	96.2777	0.217
2.012-2.078	0.264	132	0.219	2691	0.221	2889	0.954	0.968	97.7155	0.208
2.078-2.151	0.272	101	0.215	2575	0.217	2758	0.952	0.97	97.0268	0.206
2.151-2.232	0.262	130	0.202	2572	0.205	2777	0.957	0.974	97.2992	0.192
2.232-2.324	0.24	139	0.195	2336	0.197	2530	0.962	0.977	97.8261	0.185
2.324-2.427	0.215	126	0.192	2292	0.193	2474	0.969	0.977	97.7365	0.181
2.427-2.545	0.237	114	0.198	2252	0.2	2420	0.967	0.976	97.7686	0.19
2.545-2.683	0.262	111	0.201	2027	0.204	2222	0.959	0.974	96.2196	0.195
2.683-2.845	0.252	120	0.215	1955	0.217	2136	0.959	0.97	97.1442	0.209
2.845-3.042	0.206	98	0.218	1854	0.217	2011	0.966	0.972	97.0661	0.217
3.042-3.285	0.285	84	0.228	1747	0.23	1881	0.952	0.97	97.3418	0.229
3.285-3.598	0.246	89	0.225	1576	0.226	1719	0.965	0.971	96.8586	0.226
3.598-4.022	0.217	69	0.194	1414	0.195	1540	0.968	0.976	96.2987	0.202
4.022-4.643	0.194	64	0.18	1265	0.18	1366	0.976	0.979	97.2914	0.189
4.643-5.684	0.249	57	0.223	1057	0.224	1152	0.964	0.97	96.7014	0.237
5.684-8.025	0.214	48	0.22	827	0.22	894	0.983	0.976	97.8747	0.238
8.025-100.35	0.211	31	0.202	460	0.203	500	0.979	0.978	98.2	0.238

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	1.8271	-0.2501	0.7607	0.9842	-0.4952	1.4368	-0.0117	0.0606	-0.0274	0.0022	-0.01	-0.0687	0.0507	0.023	0.0217	0.04	-0.0033	0.0267	0.0032	-0.0094	0.0705	-5.4076	-21.5866	29.6886
2	1.0111	-0.1092	-0.4301	2.414	0.8268	1.1609	-0.0312	0.0055	-0.0702	0.1067	-0.0237	0.0191	0.0637	0.013	0.0549	0.0438	0.0007	0.0067	0.0197	0.0136	0.0692	-17.0727	-4.6235	54.249
3	0.866	-0.6338	0.4086	0.4843	-0.1874	3.4636	-0.0224	-0.087	0.0678	-0.0087	0.0255	-0.0035	-0.2555	-0.2491	-0.0031	0.2224	0.0329	-0.0402	0.2012	-0.0184	0.1805	-33.0526	1.4824	-17.8469
4	1.8724	0.3411	1.1557	1.5202	-0.0402	3.3157	-0.0545	0.1685	-0.0566	-0.1371	0.048	0.0847	0.0223	-0.072	0.0065	0.0914	0.0087	0.0005	0.1153	-0.031	0.0884	-16.2436	-13.5821	3.2033

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	ALL	Ap	0 - 125
2	X-RAY DIFFRACTION	2	ALL	Bp	1 - 126
3	X-RAY DIFFRACTION	3	ALL	Dp	1 - 201
4	X-RAY DIFFRACTION	4	ALL	Cp	1 - 201

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