PDB-9gqk: The FK1 domain of FKBP51 in complex with the macrocyclic SAFit an...

ID or keywords:

Entry

Database: PDB / ID: 9gqk

Title

The FK1 domain of FKBP51 in complex with the macrocyclic SAFit analog m5(11,5)-(E)-OH

Components

Peptidyl-prolyl cis-trans isomerase FKBP5

Keywords

ISOMERASE / FKBP / Inhibitor / SAFIT / Macrocycle / Complex

Function / homology

Function and homology information

Modulation of host responses by IFN-stimulated genes / response to alcohol / FK506 binding / MECP2 regulates neuronal receptors and channels / : / heat shock protein binding / ESR-mediated signaling / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / response to cocaine / response to bacterium ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.7 Å

Authors

Meyners, C. / Spiske, M. / Hausch, F.

Funding support

Germany, 2items

Citation

Journal: Angew.Chem.Int.Ed.Engl. / Year: 2025
Title: Conformationally Restricted Macrocycles as Improved FKBP51 Inhibitors Enabled by Systematic Linker Derivatization.
Authors: Spiske, M. / Meyners, C. / Bauder, M. / Repity, M. / Brudy, C. / Sugiarto, W.O. / Achaq, H. / Geiger, T.M. / Hausch, F.

History

Deposition	Sep 9, 2024	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Jan 15, 2025	Provider: repository / Type: Initial release
Revision 1.1	Mar 12, 2025	Group: Database references / Category: citation Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2	Mar 19, 2025	Group: Database references / Category: citation / citation_author Item: _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	9gqk.cif.gz	243.2 KB	Display	PDBx/mmCIF format
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Validation report

Summary document	9gqk_validation.pdf.gz	1.2 MB	Display	wwPDB validaton report
Full document	9gqk_full_validation.pdf.gz	1.2 MB	Display
Data in XML	9gqk_validation.xml.gz	14.7 KB	Display
Data in CIF	9gqk_validation.cif.gz	19.1 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/gq/9gqk ftp://data.pdbj.org/pub/pdb/validation_reports/gq/9gqk	HTTPS FTP

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Related structure data

Related structure data	9gq2C 9gq3C 9gq4C 9gq5C 9gq6C 9gq7C 9gq8C 9gq9C 9gqaC 9gqbC 9gqcC 9gqdC 9gqeC 9gqfC 9gqgC 9gqhC 9gqiC 9gqjC 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	#141 - Sep 2011 O-GlcNAc Transferase similarity (6) #230 - Feb 2019 Initiation Factor eIF4E similarity (5) #45 - Sep 2003 Estrogen Receptor similarity (1) #166 - Oct 2013 Proteasome similarity (3) #258 - Jun 2021 Glucocorticoid Receptor and Dexamethasone similarity (1) #92 - Aug 2007 Anabolic Steroids similarity (1) #126 - Jun 2010 Epidermal Growth Factor similarity (1) #208 - Apr 2017 Glucose Transporters similarity (1) #217 - Jan 2018 Opioid Receptors similarity (1) #163 - Jul 2013 HIV Capsid similarity (1) #245 - May 2020 Spliceosomes similarity (1)

PDB pages

PDBj /

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NCBI

Related items in Molecule of the Month

#141 - Sep 2011
O-GlcNAc Transferase
similarity (6)
#230 - Feb 2019
Initiation Factor eIF4E
similarity (5)
#45 - Sep 2003
Estrogen Receptor
similarity (1)
#166 - Oct 2013
Proteasome
similarity (3)
#258 - Jun 2021
Glucocorticoid Receptor and Dexamethasone
similarity (1)
#92 - Aug 2007
Anabolic Steroids
similarity (1)
#126 - Jun 2010
Epidermal Growth Factor
similarity (1)
#208 - Apr 2017
Glucose Transporters
similarity (1)
#217 - Jan 2018
Opioid Receptors
similarity (1)
#163 - Jul 2013
HIV Capsid
similarity (1)
#245 - May 2020
Spliceosomes
similarity (1)

Deposited unit

B: Peptidyl-prolyl cis-trans isomerase FKBP5

A: Peptidyl-prolyl cis-trans isomerase FKBP5

hetero molecules

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

1

B: Peptidyl-prolyl cis-trans isomerase FKBP5

hetero molecules

defined by author
14.6 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

A: Peptidyl-prolyl cis-trans isomerase FKBP5

hetero molecules

defined by author
14.6 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	49.056, 49.056, 196.83
Angle α, β, γ (deg.)	90, 90, 120
Int Tables number	154
Space group name H-M	P3₂21

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	B
2	1	A

NCS domain segments:

Component-ID: 1 / Ens-ID: 1 / Beg auth comp-ID: GLY / Beg label comp-ID: GLY / End auth comp-ID: GLU / End label comp-ID: GLU / Auth seq-ID: 13 - 140 / Label seq-ID: 1 - 128

Dom-ID	Auth asym-ID	Label asym-ID
1	B	A
2	A	B

NCS ensembles : (Details: Local NCS retraints between domains: 1 2)

#1: Protein	Peptidyl-prolyl cis-trans isomerase FKBP5 / PPIase FKBP5 / 51 kDa FK506-binding protein / FKBP-51 / 54 kDa progesterone receptor-associated ...PPIase FKBP5 / 51 kDa FK506-binding protein / FKBP-51 / 54 kDa progesterone receptor-associated immunophilin / Androgen-regulated protein 6 / FF1 antigen / FK506-binding protein 5 / FKBP-5 / FKBP54 / p54 / HSP90-binding immunophilin / Rotamase Mass: 14004.026 Da / Num. of mol.: 2 / Mutation: A19T, C103A, C107I Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FKBP5, AIG6, FKBP51 Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria) References: UniProt: Q13451, peptidylprolyl isomerase
#2: Chemical	ChemComp-A1IOE / (2~{S},9~{S},12~{R},13~{S},14~{E},18~{S})-2-cyclohexyl-22,23-dimethoxy-12,18-dimethyl-13-oxidanyl-11,17,20-trioxa-4-azatricyclo[19.3.1.0^{4,9}]pentacosa-1(25),14,21,23-tetraene-3,10-dione Mass: 559.691 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₃₁H₄₅NO₈ / Feature type: SUBJECT OF INVESTIGATION
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 91 / 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: 2.44 Å³/Da / Density % sol: 49.61 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop Details: 18% PEG3350, 0.2M ammonium acetate, 0.1M HEPES-NaOH pH 7.5, 10% glycol

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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: Jun 26, 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: 1.7→42.48 Å / Num. obs: 31151 / % possible obs: 99.2 % / Redundancy: 10.8 % / CC_1/2: 1 / R_merge(I) obs: 0.053 / R_pim(I) all: 0.023 / R_rim(I) all: 0.058 / Χ²: 1.04 / Net I/σ(I): 18.8

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
9-42.48	8.4	0.028	53.2	285	0.999	0.012	0.03	0.83	99.8
1.7-1.73	6.2	1.406	1.1	1452	0.407	0.871	1.667	1.12	90.2

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0430 (refmacat 0.4.82)	refinement
autoXDS		data reduction
Aimless		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.7→42.48 Å / Cor.coef. F_o:F_c: 0.946 / Cor.coef. F_o:F_c free: 0.931 / SU B: 7.972 / SU ML: 0.127 / Cross valid method: THROUGHOUT / ESU R: 0.128 / ESU R Free: 0.13
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2874	1500	4.832 %
R_work	0.2398	29545	-
all	0.242	-	-
obs	-	31045	98.989 %

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: 43.353 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.342 Å²	-0.171 Å²	-0 Å²
2-	-	-0.342 Å²	0 Å²
3-	-	-	1.108 Å²

Refinement step

Cycle: LAST / Resolution: 1.7→42.48 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1851	0	80	91	2022

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.015	0.012	1975
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	1845
X-RAY DIFFRACTION	r_angle_refined_deg	2.413	1.823	2674
X-RAY DIFFRACTION	r_angle_other_deg	0.808	1.744	4287
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	8.824	5	248
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	28.432	12.5	20
X-RAY DIFFRACTION	r_dihedral_angle_other_2_deg	1.802	5	2
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	13.528	10	298
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	15.95	10	66
X-RAY DIFFRACTION	r_chiral_restr	0.121	0.2	301
X-RAY DIFFRACTION	r_gen_planes_refined	0.013	0.02	2236
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	404
X-RAY DIFFRACTION	r_nbd_refined	0.214	0.2	359
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.204	0.2	1737
X-RAY DIFFRACTION	r_nbtor_refined	0.188	0.2	985
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.099	0.2	1045
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.156	0.2	89
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_other	0.138	0.2	1
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.115	0.2	9
X-RAY DIFFRACTION	r_nbd_other	0.146	0.2	40
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.058	0.2	7
X-RAY DIFFRACTION	r_mcbond_it	2.863	2.172	1004
X-RAY DIFFRACTION	r_mcbond_other	2.863	2.173	1004
X-RAY DIFFRACTION	r_mcangle_it	3.521	3.891	1248
X-RAY DIFFRACTION	r_mcangle_other	3.52	3.893	1249
X-RAY DIFFRACTION	r_scbond_it	3.19	2.293	971
X-RAY DIFFRACTION	r_scbond_other	3.189	2.292	972
X-RAY DIFFRACTION	r_scangle_it	4.188	4.139	1426
X-RAY DIFFRACTION	r_scangle_other	4.187	4.138	1427
X-RAY DIFFRACTION	r_lrange_it	5.678	20.998	2151
X-RAY DIFFRACTION	r_lrange_other	5.657	20.782	2136
X-RAY DIFFRACTION	r_ncsr_local_group_1	0.132	0.05	3502

Refine LS restraints NCS

Ens-ID	Dom-ID	Auth asym-ID	Refine-ID	Type	Rms dev position (Å)	Weight position
1	1	B	X-RAY DIFFRACTION	Local ncs	0.13189	0.05007
1	2	A	X-RAY DIFFRACTION	Local ncs	0.13189	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
1.7-1.744	0.328	104	0.353	1948	0.352	2249	0.908	0.9	91.2405	0.351
1.744-1.792	0.372	111	0.332	2006	0.334	2188	0.888	0.915	96.755	0.327
1.792-1.844	0.27	118	0.268	2044	0.268	2172	0.947	0.948	99.5396	0.258
1.844-1.9	0.275	95	0.27	1996	0.27	2091	0.939	0.948	100	0.252
1.9-1.963	0.433	105	0.347	1964	0.351	2080	0.876	0.918	99.4712	0.326
1.963-2.031	0.304	92	0.252	1866	0.255	1958	0.941	0.956	100	0.234
2.031-2.108	0.3	99	0.257	1757	0.26	1856	0.934	0.954	100	0.24
2.108-2.194	0.327	110	0.262	1739	0.266	1849	0.926	0.951	100	0.246
2.194-2.291	0.346	77	0.269	1666	0.272	1768	0.932	0.954	98.586	0.247
2.291-2.402	0.304	81	0.242	1623	0.245	1704	0.941	0.962	100	0.228
2.402-2.532	0.261	67	0.228	1556	0.23	1623	0.953	0.966	100	0.219
2.532-2.685	0.24	68	0.24	1459	0.24	1527	0.961	0.962	100	0.234
2.685-2.869	0.31	66	0.248	1398	0.25	1465	0.951	0.958	99.9317	0.244
2.869-3.098	0.292	77	0.247	1275	0.25	1352	0.948	0.957	100	0.251
3.098-3.392	0.355	45	0.255	1212	0.259	1257	0.933	0.954	100	0.262
3.392-3.789	0.234	42	0.23	1110	0.231	1153	0.978	0.971	99.9133	0.239
3.789-4.37	0.191	45	0.185	973	0.185	1018	0.98	0.98	100	0.205
4.37-5.338	0.255	40	0.199	862	0.201	902	0.964	0.976	100	0.23
5.338-7.49	0.333	34	0.245	663	0.248	697	0.954	0.969	100	0.276
7.49-42.48	0.329	24	0.248	430	0.252	454	0.942	0.939	100	0.319

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	2.0864	0.712	0.0326	3.3377	-0.4626	4.375	-0.169	0.0405	-0.2672	-0.0541	0.146	0.2515	0.2203	-0.1903	0.023	0.028	-0.0204	0.0206	0.0721	0.0402	0.0935	8.7876	-16.4392	28.183
2	3.2072	-0.4873	0.2447	8.578	1.7496	3.7777	-0.2011	-0.0205	-0.0564	-0.9826	0.4749	-1.2305	-0.4248	0.0749	-0.2738	0.2572	-0.1242	0.0828	0.0708	-0.0251	0.2237	18.4763	-0.5963	3.3514

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	ALL	B	13 - 201
2	X-RAY DIFFRACTION	2	ALL	A	13 - 201

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