PDB-29ql: FKBP12 in complex with bifunctional ligand a1d and the second bro...

ID or keywords:

Entry

Database: PDB / ID: 29ql

Title

FKBP12 in complex with bifunctional ligand a1d and the second 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: 2.1 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	Mar 30, 2026	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Sep 30, 2026	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	29ql.cif.gz	187.9 KB	Display	PDBx/mmCIF format
PDB format	pdb29ql.ent.gz		Display	PDB format
PDBx/mmJSON format	29ql.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/9q/29ql ftp://data.pdbj.org/pub/pdb/validation_reports/9q/29ql	HTTPS FTP

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Related structure data

Related structure data	9qw8C 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

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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

60.9 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
31.4 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Bromodomain-containing protein 4

hetero molecules

C: Peptidyl-prolyl cis-trans isomerase FKBP1A

hetero molecules

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

3

C: Peptidyl-prolyl cis-trans isomerase FKBP1A

hetero molecules

B: Bromodomain-containing protein 4

hetero molecules

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

Unit cell

Length a, b, c (Å)	80.422, 80.422, 212.044
Angle α, β, γ (deg.)	90, 90, 90
Int Tables number	96
Space group name H-M	P4₃2₁2

Components on special symmetry positions

ID	Model	Components
1	1	C-335- HOH

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	LYS	LYS	ASP	ASP	A	A	349 - 459	19 - 129
2	1	1	LYS	LYS	ASP	ASP	B	B	349 - 459	19 - 129
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

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Protein , 2 types, 4 molecules ABCD

#1: Protein	Bromodomain-containing protein 4 / Protein HUNK1 Mass: 15060.332 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

#1: Protein

Bromodomain-containing protein 4 / Protein HUNK1

Mass: 15060.332 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 ...

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

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Non-polymers , 4 types, 154 molecules

#3: Chemical	ChemComp-TEW / 6-tungstotellurate(VI) Mass: 1614.626 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: O₂₄TeW₆
#4: 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
#5: Chemical	ChemComp-MES / 2-(N-MORPHOLINO)-ETHANESULFONIC ACID Mass: 195.237 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₆H₁₃NO₄S / Comment: pH buffer*YM
#6: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 148 / Source method: isolated from a natural source / Formula: H₂O

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Details

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: 3.19 Å³/Da / Density % sol: 61.41 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop Details: 18% PEG3350, 0.2M ammonium thiocyanate, 0.1M MES pH 6.5, 5 mM TEW

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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 X 6M / Detector: PIXEL / Date: Apr 10, 2025

Radiation

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

Radiation wavelength

Wavelength: 0.9184 Å / Relative weight: 1

Reflection

Resolution: 2.1→44.31 Å / Num. obs: 41683 / % possible obs: 100 % / Redundancy: 19 % / CC_1/2: 0.998 / R_merge(I) obs: 0.191 / R_pim(I) all: 0.059 / R_rim(I) all: 0.2 / Χ²: 1.19 / Net I/σ(I): 12.2

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
8.91-44.31	19.2	0.13	34.3	665	0.998	0.038	0.135	1.09	99.4
2.1-2.16	13.9	1.151	1.4	3338	0.896	0.45	1.239	1.52	99.9

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0430 (refmacat 0.4.126)	refinement
autoXDS		data reduction
Aimless		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.1→44.3 Å / Cor.coef. F_o:F_c: 0.909 / Cor.coef. F_o:F_c free: 0.862 / SU B: 5.744 / SU ML: 0.141 / Cross valid method: THROUGHOUT / ESU R: 0.214 / ESU R Free: 0.187
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2753	1943	4.891 %
R_work	0.2454	37783	-
all	0.247	-	-
obs	-	39726	95.472 %

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: 24.487 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	1.509 Å²	-0 Å²	-0 Å²
2-	-	1.509 Å²	-0 Å²
3-	-	-	-3.017 Å²

Refinement step

Cycle: LAST / Resolution: 2.1→44.3 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3359	0	207	148	3714

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.018	0.012	3699
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	3239
X-RAY DIFFRACTION	r_angle_refined_deg	3.828	1.95	5009
X-RAY DIFFRACTION	r_angle_other_deg	0.378	1.76	7516
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.057	5	432
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	16.354	5	29
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	13.608	10	558
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	14.005	10	148
X-RAY DIFFRACTION	r_chiral_restr	0.058	0.2	514
X-RAY DIFFRACTION	r_gen_planes_refined	0.004	0.02	4155
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	789
X-RAY DIFFRACTION	r_nbd_refined	0.201	0.2	725
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.184	0.2	2938
X-RAY DIFFRACTION	r_nbtor_refined	0.178	0.2	1809
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.083	0.2	1718
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.147	0.2	173
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.182	0.2	9
X-RAY DIFFRACTION	r_nbd_other	0.141	0.2	61
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.26	0.2	7
X-RAY DIFFRACTION	r_mcbond_it	1.016	2.436	1740
X-RAY DIFFRACTION	r_mcbond_other	1.015	2.436	1740
X-RAY DIFFRACTION	r_mcangle_it	1.769	4.368	2168
X-RAY DIFFRACTION	r_mcangle_other	1.769	4.37	2169
X-RAY DIFFRACTION	r_scbond_it	1.539	2.564	1959
X-RAY DIFFRACTION	r_scbond_other	1.542	2.565	1953
X-RAY DIFFRACTION	r_scangle_it	2.069	4.665	2823
X-RAY DIFFRACTION	r_scangle_other	2.069	4.665	2824
X-RAY DIFFRACTION	r_lrange_it	3.356	22.619	4089
X-RAY DIFFRACTION	r_lrange_other	3.337	22.45	4064
X-RAY DIFFRACTION	r_ncsr_local_group_1	0.064	0.05	3621
X-RAY DIFFRACTION	r_ncsr_local_group_2	0.083	0.05	3137

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	0.06388	0.0501
1	2	B	X-RAY DIFFRACTION	Local ncs	0.06388	0.0501
2	3	C	X-RAY DIFFRACTION	Local ncs	0.08278	0.0501
2	4	D	X-RAY DIFFRACTION	Local ncs	0.08278	0.0501

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
2.1-2.154	0.423	123	0.378	2590	0.38	3005	0.863	0.88	90.2829	0.358
2.154-2.213	0.351	145	0.337	2519	0.338	2932	0.909	0.91	90.8595	0.314
2.213-2.277	0.356	124	0.344	2496	0.344	2857	0.908	0.912	91.7046	0.315
2.277-2.347	0.316	113	0.313	2439	0.313	2768	0.911	0.926	92.1965	0.285
2.347-2.424	0.295	134	0.281	2390	0.281	2717	0.941	0.945	92.8966	0.256
2.424-2.509	0.285	101	0.261	2371	0.262	2621	0.946	0.955	94.3151	0.238
2.509-2.603	0.342	119	0.25	2283	0.254	2514	0.927	0.958	95.5449	0.227
2.603-2.709	0.242	111	0.24	2248	0.24	2447	0.961	0.964	96.4038	0.215
2.709-2.829	0.316	128	0.231	2135	0.236	2335	0.947	0.965	96.9165	0.21
2.829-2.967	0.26	105	0.218	2068	0.22	2238	0.96	0.969	97.0956	0.198
2.967-3.126	0.25	111	0.228	1992	0.229	2149	0.961	0.967	97.8595	0.21
3.126-3.315	0.261	91	0.24	1905	0.241	2039	0.96	0.966	97.8911	0.224
3.315-3.542	0.24	89	0.229	1811	0.229	1923	0.965	0.971	98.8039	0.218
3.542-3.824	0.265	104	0.229	1690	0.231	1810	0.958	0.969	99.116	0.218
3.824-4.186	0.248	78	0.193	1561	0.196	1662	0.967	0.978	98.6161	0.186
4.186-4.675	0.164	68	0.172	1433	0.171	1514	0.988	0.983	99.1413	0.168
4.675-5.388	0.225	66	0.194	1287	0.195	1360	0.969	0.979	99.4853	0.19
5.388-6.575	0.244	55	0.236	1110	0.236	1168	0.979	0.972	99.7431	0.231
6.575-9.197	0.258	58	0.231	885	0.232	950	0.954	0.969	99.2632	0.231
9.197-44.3	0.443	20	0.298	570	0.302	593	0.936	0.944	99.4941	0.35

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