PDB-9gq4: The FK1 domain of FKBP51 in complex with the macrocyclic SAFit an...

ID or keywords:

Entry

Database: PDB / ID: 9gq4

Title

The FK1 domain of FKBP51 in complex with the macrocyclic SAFit analog p5(3,1)-(E)

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 / peptidylprolyl isomerase ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.8 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	9gq4.cif.gz	240.2 KB	Display	PDBx/mmCIF format
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Validation report

Summary document	9gq4_validation.pdf.gz	1.2 MB	Display	wwPDB validaton report
Full document	9gq4_full_validation.pdf.gz	1.2 MB	Display
Data in XML	9gq4_validation.xml.gz	15.8 KB	Display
Data in CIF	9gq4_validation.cif.gz	20.5 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/gq/9gq4 ftp://data.pdbj.org/pub/pdb/validation_reports/gq/9gq4	HTTPS FTP

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Related structure data

Related structure data	9gq2C 9gq3C 9gq5C 9gq6C 9gq7C 9gq8C 9gq9C 9gqaC 9gqbC 9gqcC 9gqdC 9gqeC 9gqfC 9gqgC 9gqhC 9gqiC 9gqjC 9gqkC 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

A: Peptidyl-prolyl cis-trans isomerase FKBP5

B: Peptidyl-prolyl cis-trans isomerase FKBP5

hetero molecules

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

1

A: Peptidyl-prolyl cis-trans isomerase FKBP5

hetero molecules

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

2

B: Peptidyl-prolyl cis-trans isomerase FKBP5

hetero molecules

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

Unit cell

Length a, b, c (Å)	48.667, 48.667, 192.723
Angle α, β, γ (deg.)	90, 90, 120
Int Tables number	154
Space group name H-M	P3₂21

Components on special symmetry positions

ID	Model	Components
1	1	B-345- HOH

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	A
2	1	B

NCS domain segments:

Component-ID: 1 / Ens-ID: 1 / Beg auth comp-ID: THR / Beg label comp-ID: THR / End auth comp-ID: GLY / End label comp-ID: GLY / Auth seq-ID: 17 - 139 / Label seq-ID: 5 - 127

Dom-ID	Auth asym-ID	Label asym-ID
1	A	A
2	B	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-A1IN2 / (2~{S},9~{S},16~{E})-2-cyclohexyl-21,24-dimethoxy-11,14,19-trioxa-4-azatricyclo[18.2.2.0^{4,9}]tetracosa-1(23),16,20(24),21-tetraene-3,10-dione Mass: 501.612 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₈H₃₉NO₇ / Feature type: SUBJECT OF INVESTIGATION
#3: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 133 / 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: 2.35 Å³/Da / Density % sol: 47.71 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, hanging drop Details: 20% PEG3350, 0.2M ammonium thiocyanate, 0.1M HEPES-NaOH pH 7.5

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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: Mar 18, 2022

Radiation

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

Radiation wavelength

Wavelength: 0.9184 Å / Relative weight: 1

Reflection

Resolution: 1.8→48.18 Å / Num. obs: 25641 / % possible obs: 100 % / Redundancy: 10.6 % / CC_1/2: 1 / R_merge(I) obs: 0.037 / R_pim(I) all: 0.017 / R_rim(I) all: 0.04 / Χ²: 0.99 / Net I/σ(I): 29.2

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
9-48.18	8.4	0.019	75.8	273	1	0.008	0.021	0.76	99.3
1.8-1.84	10.9	0.525	4.3	1479	0.926	0.239	0.577	0.99	100

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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: 1.8→42.182 Å / Cor.coef. F_o:F_c: 0.948 / Cor.coef. F_o:F_c free: 0.938 / SU B: 6.728 / SU ML: 0.106 / Cross valid method: THROUGHOUT / ESU R: 0.149 / ESU R Free: 0.131
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2466	1300	5.083 %
R_work	0.229	24274	-
all	0.23	-	-
obs	-	25574	99.949 %

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: 40.092 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.04 Å²	-0.02 Å²	-0 Å²
2-	-	-0.04 Å²	0 Å²
3-	-	-	0.131 Å²

Refinement step

Cycle: LAST / Resolution: 1.8→42.182 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	1829	0	72	133	2034

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.014	0.012	1945
X-RAY DIFFRACTION	r_bond_other_d	0.006	0.016	1786
X-RAY DIFFRACTION	r_angle_refined_deg	2.123	1.848	2636
X-RAY DIFFRACTION	r_angle_other_deg	1.236	1.811	4156
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.67	5	250
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	10.108	5	4
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	11.371	10	288
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	13.945	10	63
X-RAY DIFFRACTION	r_chiral_restr	0.104	0.2	295
X-RAY DIFFRACTION	r_chiral_restr_other	1.705	0.2	30
X-RAY DIFFRACTION	r_gen_planes_refined	0.01	0.02	2217
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	399
X-RAY DIFFRACTION	r_nbd_refined	0.204	0.2	370
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.197	0.2	1730
X-RAY DIFFRACTION	r_nbtor_refined	0.18	0.2	1013
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.095	0.2	1004
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.151	0.2	94
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.124	0.2	4
X-RAY DIFFRACTION	r_nbd_other	0.135	0.2	31
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.097	0.2	10
X-RAY DIFFRACTION	r_mcbond_it	2.582	2.363	1012
X-RAY DIFFRACTION	r_mcbond_other	2.581	2.363	1012
X-RAY DIFFRACTION	r_mcangle_it	3.458	4.24	1258
X-RAY DIFFRACTION	r_mcangle_other	3.457	4.238	1259
X-RAY DIFFRACTION	r_scbond_it	2.866	2.431	933
X-RAY DIFFRACTION	r_scbond_other	2.864	2.431	934
X-RAY DIFFRACTION	r_scangle_it	3.891	4.405	1378
X-RAY DIFFRACTION	r_scangle_other	3.89	4.404	1379
X-RAY DIFFRACTION	r_lrange_it	6.173	22.499	2164
X-RAY DIFFRACTION	r_lrange_other	6.197	22.156	2146
X-RAY DIFFRACTION	r_ncsr_local_group_1	0.12	0.05	3259

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	0.12039	0.05007
1	2	B	X-RAY DIFFRACTION	Local ncs	0.12039	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
1.8-1.847	0.3	82	0.272	1757	0.273	1839	0.944	0.951	100	0.251
1.847-1.897	0.242	82	0.255	1697	0.255	1780	0.96	0.957	99.9438	0.233
1.897-1.952	0.299	74	0.266	1715	0.267	1789	0.944	0.954	100	0.244
1.952-2.012	0.275	93	0.26	1613	0.261	1706	0.953	0.954	100	0.236
2.012-2.078	0.311	89	0.251	1530	0.255	1619	0.932	0.959	100	0.228
2.078-2.151	0.28	90	0.245	1527	0.247	1617	0.953	0.96	100	0.227
2.151-2.232	0.282	68	0.241	1501	0.243	1570	0.948	0.962	99.9363	0.219
2.232-2.322	0.257	80	0.251	1415	0.251	1495	0.961	0.96	100	0.23
2.322-2.425	0.282	87	0.241	1360	0.244	1447	0.952	0.963	100	0.222
2.425-2.543	0.273	65	0.242	1315	0.244	1380	0.955	0.962	100	0.225
2.543-2.68	0.333	57	0.24	1263	0.244	1320	0.934	0.963	100	0.227
2.68-2.842	0.347	72	0.25	1183	0.255	1255	0.922	0.958	100	0.24
2.842-3.038	0.234	72	0.25	1111	0.249	1184	0.967	0.958	99.9155	0.249
3.038-3.279	0.329	54	0.227	1047	0.232	1102	0.944	0.967	99.9093	0.227
3.279-3.59	0.215	56	0.232	958	0.231	1014	0.972	0.971	100	0.239
3.59-4.01	0.19	51	0.199	901	0.199	952	0.979	0.979	100	0.209
4.01-4.624	0.154	38	0.167	794	0.166	834	0.986	0.984	99.7602	0.188
4.624-5.646	0.177	41	0.183	687	0.183	730	0.983	0.981	99.726	0.214
5.646-7.914	0.222	36	0.269	542	0.266	579	0.967	0.966	99.8273	0.303
7.914-42.182	0.333	13	0.27	358	0.272	374	0.89	0.937	99.1979	0.369

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	2.6358	-0.1722	0.3231	3.3261	0.9506	3.8206	-0.1462	0.0979	0.4141	0.1213	0.0133	-0.2215	-0.0362	-0.0368	0.1329	0.0267	-0.0179	-0.0201	0.0184	0.0008	0.0913	-9.614	15.398	28.1011
2	3.7544	-1.1812	0.5043	5.7083	-0.2663	3.6553	-0.0412	-0.0178	-0.0423	-0.5203	0.1221	0.6695	0.2058	-0.225	-0.0809	0.1634	-0.0829	-0.011	0.0516	-0.0161	0.1158	-18.4703	-0.8048	3.3482

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	ALL	A	17 - 201
2	X-RAY DIFFRACTION	2	ALL	B	13 - 201

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