PDB-9eu0: Crystal structure of Danio rerio HDAC6 CD2 in complex with hydrol...

ID or keywords:

Entry

Database: PDB / ID: 9eu0

Title

Crystal structure of Danio rerio HDAC6 CD2 in complex with hydrolyzed DFMO-inhibitor (ITF7209)

Components

Histone deacetylase 6

Keywords

HYDROLASE / HISTONE DEACETYLASE / COMPLEX WITH HYDRAZIDE / NON-HYDROXAMATE ZINC BINDING GROUP / MECHANISM-BASED INHIBITOR

Function / homology

Function and homology information

Aggrephagy / tubulin deacetylase activity / swimming behavior / definitive hemopoiesis / protein lysine deacetylase activity / histone deacetylase activity / potassium ion binding / histone deacetylase complex / hematopoietic progenitor cell differentiation / epigenetic regulation of gene expression ...
Similarity search - Function

Biological species

Danio rerio (zebrafish)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.86 Å

Authors

Bebel, A. / Cellupica, E. / Stevenazzi, A. / Sandrone, G. / Vergani, B. / Caprini, G.

Funding support

1items

Citation

Journal: Int J Mol Sci / Year: 2024
Title: Mechanistic and Structural Insights on Difluoromethyl-1,3,4-oxadiazole Inhibitors of HDAC6.
Authors: Cellupica, E. / Gaiassi, A. / Rocchio, I. / Rovelli, G. / Pomarico, R. / Sandrone, G. / Caprini, G. / Cordella, P. / Cukier, C. / Fossati, G. / Marchini, M. / Bebel, A. / Airoldi, C. / ...

History

Deposition	Mar 27, 2024	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Dec 4, 2024	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	9eu0.cif.gz	295.5 KB	Display	PDBx/mmCIF format
PDB format	pdb9eu0.ent.gz		Display	PDB format
PDBx/mmJSON format	9eu0.json.gz		Tree view	PDBx/mmJSON format
Others	Other downloads

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Validation report

Summary document	9eu0_validation.pdf.gz	1 MB	Display	wwPDB validaton report
Full document	9eu0_full_validation.pdf.gz	1 MB	Display
Data in XML	9eu0_validation.xml.gz	35.6 KB	Display
Data in CIF	9eu0_validation.cif.gz	48.9 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/eu/9eu0 ftp://data.pdbj.org/pub/pdb/validation_reports/eu/9eu0	HTTPS FTP

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Related structure data

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

Deposited unit

A: Histone deacetylase 6

B: Histone deacetylase 6

hetero molecules

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

1

A: Histone deacetylase 6

hetero molecules

defined by author
Evidence: gel filtration
41.1 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Histone deacetylase 6

hetero molecules

defined by author
Evidence: gel filtration
40.8 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	74.71, 91.56, 96.13
Angle α, β, γ (deg.)	90, 90, 90
Int Tables number	19
Space group name H-M	P2₁2₁2₁

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Protein , 1 types, 2 molecules AB

#1: Protein	Histone deacetylase 6 Mass: 40342.535 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Danio rerio (zebrafish) / Gene: hdac6 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: F8W4B7

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Non-polymers , 5 types, 398 molecules

#2: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical	ChemComp-K / POTASSIUM ION Mass: 39.098 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: K
#4: Chemical	ChemComp-EPE / 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / HEPES Mass: 238.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₈H₁₈N₂O₄S / Comment: pH buffer*YM
#5: Chemical	ChemComp-A1H7I / ~{N}'-[2,2-bis(fluoranyl)ethanoyl]-5-[(4-~{tert}-butyl-1,2,3-triazol-1-yl)methyl]thiophene-2-carbohydrazide Mass: 357.379 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: C₁₄H₁₇F₂N₅O₂S / Feature type: SUBJECT OF INVESTIGATION
#6: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 389 / 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: 2.06 Å³/Da / Density % sol: 40.17 %
Crystal grow	Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5.5 Details: 0.1% (w/v) nOctyl-b-D-glucoside, 0.1 M Sodium citrate tribasic dihydrate pH 5.5, 21% (w/v) PEG 3350

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: SOLEIL / Beamline: PROXIMA 1 / Wavelength: 0.979 Å
Detector	Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 3, 2023
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.979 Å / Relative weight: 1
Reflection	Resolution: 1.86→48.065 Å / Num. obs: 56003 / % possible obs: 99.9 % / Redundancy: 12.9 % / CC_1/2: 0.997 / Net I/σ(I): 8.67
Reflection shell	Resolution: 1.86→1.91 Å / Mean I/σ(I) obs: 1.82 / Num. unique obs: 4085 / CC_1/2: 0.792 / % possible all: 99.5

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0425	refinement
XDS		data reduction
XSCALE		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 1.86→48.065 Å / Cor.coef. F_o:F_c: 0.972 / Cor.coef. F_o:F_c free: 0.948 / SU B: 3.632 / SU ML: 0.104 / Cross valid method: FREE R-VALUE / ESU R: 0.153 / ESU R Free: 0.142
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2215	2801	5.002 %
R_work	0.1765	53202	-
all	0.179	-	-
obs	-	56003	99.863 %

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: 28.725 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.41 Å²	0 Å²	-0 Å²
2-	-	1.164 Å²	0 Å²
3-	-	-	-0.754 Å²

Refinement step

Cycle: LAST / Resolution: 1.86→48.065 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	5573	0	69	389	6031

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.008	0.012	5829
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.016	5342
X-RAY DIFFRACTION	r_angle_refined_deg	1.633	1.82	7918
X-RAY DIFFRACTION	r_angle_other_deg	0.571	1.748	12286
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.795	5	721
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	13.823	5	65
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	13.042	10	931
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	16.522	10	271
X-RAY DIFFRACTION	r_chiral_restr	0.083	0.2	857
X-RAY DIFFRACTION	r_chiral_restr_other	0.006	0.2	1
X-RAY DIFFRACTION	r_gen_planes_refined	0.007	0.02	7006
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	1388
X-RAY DIFFRACTION	r_nbd_refined	0.254	0.2	1313
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.19	0.2	5238
X-RAY DIFFRACTION	r_nbtor_refined	0.179	0.2	2868
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.079	0.2	2906
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.162	0.2	373
X-RAY DIFFRACTION	r_metal_ion_refined	0.154	0.2	23
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.186	0.2	16
X-RAY DIFFRACTION	r_nbd_other	0.198	0.2	68
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.229	0.2	11
X-RAY DIFFRACTION	r_mcbond_it	2.247	2.65	2875
X-RAY DIFFRACTION	r_mcbond_other	2.246	2.65	2875
X-RAY DIFFRACTION	r_mcangle_it	3.124	4.75	3599
X-RAY DIFFRACTION	r_mcangle_other	3.124	4.751	3600
X-RAY DIFFRACTION	r_scbond_it	3.225	3.067	2954
X-RAY DIFFRACTION	r_scbond_other	3.224	3.065	2954
X-RAY DIFFRACTION	r_scangle_it	4.831	5.486	4319
X-RAY DIFFRACTION	r_scangle_other	4.831	5.488	4320
X-RAY DIFFRACTION	r_lrange_it	6.254	27.833	6757
X-RAY DIFFRACTION	r_lrange_other	6.254	27.837	6758

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
1.86-1.908	0.353	204	0.3	3870	0.302	4102	0.916	0.937	99.3174	0.283
1.908-1.96	0.282	199	0.263	3771	0.264	3974	0.943	0.954	99.8993	0.246
1.96-2.017	0.28	194	0.245	3700	0.247	3897	0.954	0.962	99.923	0.225
2.017-2.079	0.267	188	0.215	3556	0.217	3747	0.957	0.971	99.9199	0.196
2.079-2.147	0.274	184	0.205	3497	0.208	3681	0.951	0.975	100	0.186
2.147-2.222	0.246	176	0.187	3358	0.19	3534	0.96	0.98	100	0.169
2.222-2.306	0.221	171	0.176	3238	0.178	3410	0.972	0.982	99.9707	0.159
2.306-2.4	0.225	165	0.171	3146	0.174	3314	0.973	0.982	99.9095	0.155
2.4-2.506	0.234	158	0.173	3003	0.176	3161	0.97	0.984	100	0.159
2.506-2.628	0.215	152	0.171	2882	0.173	3034	0.977	0.985	100	0.16
2.628-2.77	0.246	145	0.176	2757	0.18	2903	0.963	0.983	99.9656	0.168
2.77-2.938	0.251	136	0.175	2586	0.178	2723	0.966	0.983	99.9633	0.171
2.938-3.14	0.192	130	0.169	2457	0.17	2587	0.978	0.984	100	0.169
3.14-3.39	0.211	121	0.168	2310	0.17	2431	0.97	0.983	100	0.175
3.39-3.712	0.204	111	0.154	2109	0.156	2223	0.977	0.987	99.8651	0.168
3.712-4.147	0.196	101	0.154	1923	0.156	2026	0.978	0.987	99.9013	0.174
4.147-4.782	0.16	90	0.131	1711	0.132	1808	0.987	0.991	99.6128	0.157
4.782-5.842	0.165	78	0.145	1465	0.146	1548	0.988	0.99	99.677	0.174
5.842-8.202	0.171	61	0.152	1166	0.153	1228	0.983	0.988	99.9186	0.185
8.202-48.065	0.261	37	0.2	697	0.203	745	0.917	0.976	98.5235	0.243

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