PDB-9r5n: FKBP12 in complex with binfunctional ligand b3c and the first bro...

ID or keywords:

Entry

Database: PDB / ID: 9r5n

Title

FKBP12 in complex with binfunctional ligand b3c 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 / ventricular cardiac muscle tissue morphogenesis / ryanodine receptor complex / 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 refolding / protein maturation / 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 / protein folding / regulation of inflammatory response / 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 / nucleoplasm / membrane / nucleus / cytosol / cytoplasm
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 3 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	May 9, 2025	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	May 20, 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	9r5n.cif.gz	405.9 KB	Display	PDBx/mmCIF format
PDB format	pdb9r5n.ent.gz		Display	PDB format
PDBx/mmJSON format	9r5n.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/r5/9r5n ftp://data.pdbj.org/pub/pdb/validation_reports/r5/9r5n	HTTPS FTP

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Related structure data

Related structure data	29qlC 9qw8C C: citing same article (ref.)
Similar structure data	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	#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

C: Peptidyl-prolyl cis-trans isomerase FKBP1A

D: Peptidyl-prolyl cis-trans isomerase FKBP1A

hetero molecules

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

1

A: Bromodomain-containing protein 4

D: 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

B: 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)

Unit cell

Length a, b, c (Å)	57.817, 90.513, 103.116
Angle α, β, γ (deg.)	90, 90, 90
Int Tables number	19
Space group name H-M	P2₁2₁2₁

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details (eV)
1	1	A
2	1	B
3	2	C
4	2	D

NCS domain segments:

Dom-ID	Component-ID	Ens-ID	Beg auth comp-ID	Beg label comp-ID	End auth comp-ID	End label comp-ID	Auth asym-ID	Label asym-ID	Auth seq-ID	Label seq-ID
1	1	1	THR	THR	LYS	LYS	A	A	18 - 118	19 - 119
2	1	1	THR	THR	LYS	LYS	B	B	18 - 118	19 - 119
3	2	2	GLY	GLY	GLU	GLU	C	C	1 - 107	1 - 107
4	2	2	GLY	GLY	GLU	GLU	D	D	1 - 107	1 - 107

NCS ensembles :

ID	Details (eV)
1	Local NCS retraints between domains: 1 2
2	Local NCS retraints between domains: 3 4

#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: C23V 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-A1JCU / ~{tert}-butyl 2-[(9~{S})-7-[4-[3-[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]-1,2,3-triazol-1-yl]ethoxy]ethanoylamino]prop-1-ynyl]phenyl]-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]ethanoate Mass: 1081.099 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₅₂H₅₅Cl₂N₁₁O₇S₂ / Feature type: SUBJECT OF INVESTIGATION
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: 2.5 Å³/Da / Density % sol: 50.89 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 25% PEG3350, 0.2M ammonium thiocyanate, 0.1 M Tris-HCl pH 8.8

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Data collection

Diffraction

Mean temperature: 100 K / Serial crystal experiment: N

Diffraction source

Source:

SYNCHROTRON / Site:

BESSY

/ Beamline: 14.1 / Wavelength: 0.9184 Å

Detector

Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Nov 7, 2024

Radiation

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

Radiation wavelength

Wavelength: 0.9184 Å / Relative weight: 1

Reflection

Resolution: 3→48.72 Å / Num. obs: 11367 / % possible obs: 99.9 % / Redundancy: 12.5 % / CC_1/2: 0.989 / R_merge(I) obs: 0.306 / R_pim(I) all: 0.127 / R_rim(I) all: 0.332 / Χ²: 1.04 / Net I/σ(I): 8.9

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
9-48.72	10.3	0.079	17.6	487	0.999	0.034	0.086	0.98	99.5
3-3.18	13.2	0.66	4.3	1804	0.936	0.269	0.713	0.94	100

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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: 3→48.72 Å / Cor.coef. F_o:F_c: 0.901 / Cor.coef. F_o:F_c free: 0.843 / SU B: 62.937 / SU ML: 0.498 / Cross valid method: THROUGHOUT / ESU R Free: 0.538
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.312	596	5.262 %
R_work	0.26	10730	-
all	0.263	-	-
obs	-	11326	99.789 %

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: 26.841 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-4.63 Å²	-0 Å²	0 Å²
2-	-	-0.726 Å²	0 Å²
3-	-	-	5.356 Å²

Refinement step

Cycle: LAST / Resolution: 3→48.72 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3265	0	148	0	3413

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.019	0.012	3513
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	3130
X-RAY DIFFRACTION	r_angle_refined_deg	2.67	1.83	4810
X-RAY DIFFRACTION	r_angle_other_deg	0.848	1.737	7217
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.224	5	417
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	29.593	10.294	34
X-RAY DIFFRACTION	r_dihedral_angle_other_2_deg	3.396	5	2
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	18.365	10	512
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	14.699	10	147
X-RAY DIFFRACTION	r_chiral_restr	0.128	0.2	523
X-RAY DIFFRACTION	r_gen_planes_refined	0.011	0.02	4107
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	799
X-RAY DIFFRACTION	r_nbd_refined	0.228	0.2	607
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.232	0.2	3135
X-RAY DIFFRACTION	r_nbtor_refined	0.203	0.2	1721
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.102	0.2	1955
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.169	0.2	99
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.072	0.2	4
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.21	0.2	31
X-RAY DIFFRACTION	r_nbd_other	0.235	0.2	59
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.172	0.2	6
X-RAY DIFFRACTION	r_mcbond_it	0.478	0.054	1680
X-RAY DIFFRACTION	r_mcbond_other	0.478	0.054	1680
X-RAY DIFFRACTION	r_mcangle_it	0.826	0.096	2093
X-RAY DIFFRACTION	r_mcangle_other	0.826	0.096	2094
X-RAY DIFFRACTION	r_scbond_it	0.2	0.055	1833
X-RAY DIFFRACTION	r_scbond_other	0.2	0.055	1832
X-RAY DIFFRACTION	r_scangle_it	0.501	0.102	2717
X-RAY DIFFRACTION	r_scangle_other	0.501	0.102	2718
X-RAY DIFFRACTION	r_lrange_it	0.901	0.642	14523
X-RAY DIFFRACTION	r_lrange_other	0.901	0.642	14524
X-RAY DIFFRACTION	r_ncsr_local_group_1	0.163	0.05	3157
X-RAY DIFFRACTION	r_ncsr_local_group_2	0.188	0.05	2964

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	0.16323	0.05007
1	2	B	X-RAY DIFFRACTION	Local ncs	0.16323	0.05007
2	3	C	X-RAY DIFFRACTION	Local ncs	0.18768	0.05007
2	4	D	X-RAY DIFFRACTION	Local ncs	0.18768	0.05007

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
3-3.078	0.369	46	0.322	773	0.325	819	0.894	0.914	100	0.274
3.078-3.162	0.345	36	0.322	773	0.323	810	0.914	0.924	99.8765	0.283
3.162-3.253	0.362	49	0.297	726	0.301	777	0.883	0.934	99.7426	0.247
3.253-3.353	0.374	42	0.306	707	0.31	749	0.906	0.928	100	0.263
3.353-3.462	0.375	41	0.306	699	0.309	741	0.889	0.931	99.8651	0.258
3.462-3.583	0.406	28	0.289	682	0.294	710	0.894	0.933	100	0.246
3.583-3.718	0.265	39	0.269	635	0.269	675	0.955	0.945	99.8519	0.228
3.718-3.868	0.303	34	0.225	631	0.229	665	0.946	0.967	100	0.193
3.868-4.039	0.208	43	0.214	587	0.213	630	0.973	0.969	100	0.177
4.039-4.235	0.305	29	0.2	583	0.204	612	0.917	0.974	100	0.172
4.235-4.462	0.228	23	0.215	566	0.216	592	0.966	0.971	99.4932	0.184
4.462-4.73	0.279	23	0.208	530	0.212	557	0.943	0.976	99.2819	0.176
4.73-5.054	0.231	29	0.222	480	0.223	511	0.966	0.97	99.6086	0.188
5.054-5.454	0.312	30	0.232	464	0.237	499	0.947	0.965	98.998	0.196
5.454-5.967	0.339	20	0.261	449	0.265	469	0.917	0.952	100	0.22
5.967-6.659	0.305	23	0.241	381	0.244	404	0.933	0.963	100	0.204
6.659-7.665	0.34	18	0.265	355	0.268	374	0.952	0.956	99.7326	0.222
7.665-9.33	0.322	15	0.252	307	0.255	323	0.933	0.965	99.6904	0.225
9.33-12.96	0.292	15	0.247	246	0.25	261	0.969	0.971	100	0.234
12.96-48.72	0.368	13	0.37	156	0.369	169	0.892	0.906	100	0.372

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	3.5093	0.6358	0.4209	4.3072	0.5569	1.4421	-0.0823	0.4951	-0.0279	-0.5383	0.0468	-0.1563	0.0131	0.1291	0.0355	0.2668	0.0168	0.0359	0.0816	-0.0203	0.4241	-3.2534	-14.6361	17.1883
2	3.3542	0.4225	-0.8128	4.3904	-0.9069	1.7043	-0.07	0.4241	0.2367	-0.4919	0.1485	0.1528	-0.1375	-0.1766	-0.0784	0.2554	-0.0114	-0.0597	0.1364	0.0292	0.3561	-25.3386	-10.0582	18.3573
3	5.2698	-1.5707	1.3225	3.6952	-0.9846	2.8511	0.135	0.1013	-0.3157	-0.1803	-0.1684	0.2136	0.1003	0.0367	0.0334	0.2475	0.007	0.0429	0.0081	-0.0184	0.257	-21.3495	15.3421	19.7634
4	4.9321	-0.0833	-0.5584	4.2974	-0.2389	2.2948	-0.028	-0.0118	0.5374	-0.2265	0.007	-0.1188	0.0084	-0.0141	0.0211	0.2266	0.0507	-0.0166	0.0448	-0.0013	0.2166	-7.5058	-40.2383	19.9961

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	ALL	Ap	16 - 201
2	X-RAY DIFFRACTION	2	ALL	Bp	18 - 201
3	X-RAY DIFFRACTION	3	ALL	Cp	1 - 107
4	X-RAY DIFFRACTION	4	ALL	Dp	1 - 107

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