PDB-8og8: Crystal structure of human DCAF1 WD40 repeats (Q1250L) in complex...

ID or keywords:

Entry

Database: PDB / ID: 8og8

Title

Crystal structure of human DCAF1 WD40 repeats (Q1250L) in complex with compound 3

Components

DDB1- and CUL4-associated factor 1

Keywords

TRANSFERASE / DCAF1 / E3 ligase / compound

Function / homology

Function and homology information

histone H2AT120 kinase activity / cell competition in a multicellular organism / V(D)J recombination / Cul4-RING E3 ubiquitin ligase complex / ubiquitin-like ligase-substrate adaptor activity / B cell differentiation / post-translational protein modification / nuclear estrogen receptor binding / fibrillar center / positive regulation of protein catabolic process ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.11 Å

Authors

Schroeder, M. / Vulpetti, A. / Renatus, M.

Funding support

1items

Citation

Journal: Acs Med.Chem.Lett. / Year: 2023
Title: Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field.
Authors: Vulpetti, A. / Holzer, P. / Schmiedeberg, N. / Imbach-Weese, P. / Pissot-Soldermann, C. / Hollingworth, G.J. / Radimerski, T. / Thoma, C.R. / Stachyra, T.M. / Wojtynek, M. / Maschlej, M. / ...

History

Deposition	Mar 19, 2023	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Jun 14, 2023	Provider: repository / Type: Initial release
Revision 1.1	Aug 2, 2023	Group: Database references / Category: citation Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2	Jun 19, 2024	Group: Data collection / Category: chem_comp_atom / chem_comp_bond

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	8og8.cif.gz	232.4 KB	Display	PDBx/mmCIF format
PDB format	pdb8og8.ent.gz	181.8 KB	Display	PDB format
PDBx/mmJSON format	8og8.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	8og8_validation.pdf.gz	1.6 MB	Display	wwPDB validaton report
Full document	8og8_full_validation.pdf.gz	1.6 MB	Display
Data in XML	8og8_validation.xml.gz	16.3 KB	Display
Data in CIF	8og8_validation.cif.gz	23.4 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/og/8og8 ftp://data.pdbj.org/pub/pdb/validation_reports/og/8og8	HTTPS FTP

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Related structure data

Related structure data	8og5C 8og6C 8og7C 8og9C 8ogaC 8ogbC 8ogcC 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

Deposited unit

A: DDB1- and CUL4-associated factor 1

hetero molecules

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

1

Idetical with deposited unit
defined by author

Unit cell

Length a, b, c (Å)	81.811, 81.811, 232.957
Angle α, β, γ (deg.)	90.000, 90.000, 120.000
Int Tables number	178
Space group name H-M	P6₁22

Components on special symmetry positions

ID	Model	Components
1	1	A-1503- ACT
2	1	A-1503- ACT
3	1	A-1727- HOH

#1: Protein	DDB1- and CUL4-associated factor 1 / HIV-1 Vpr-binding protein / VprBP / Serine/threonine-protein kinase VPRBP / Vpr-interacting protein Mass: 41764.824 Da / Num. of mol.: 1 / Mutation: Q1250L Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DCAF1, KIAA0800, RIP, VPRBP / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q9Y4B6, non-specific serine/threonine protein kinase
#2: Chemical	ChemComp-VM8 / 5-(2-methyl-1-phenyl-propan-2-yl)imidazo[2,1-a]isoquinoline Mass: 300.397 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₁H₂₀N₂ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-ACT / ACETATE ION Mass: 59.044 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂H₃O₂
#4: Chemical	ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂H₆O₂
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 173 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 2.69 Å³/Da / Density % sol: 54.35 %
Crystal grow	Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 / Details: 0.1M MES pH6.5, 2.13M Lithium acetate

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
Detector	Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 21, 2015
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1 Å / Relative weight: 1
Reflection	Resolution: 2.11→46.59 Å / Num. obs: 27598 / % possible obs: 100 % / Redundancy: 14.3 % / CC_1/2: 0.998 / Net I/σ(I): 14.4
Reflection shell	Resolution: 2.11→2.17 Å / Num. unique obs: 2186 / CC_1/2: 0.718

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0267	refinement
Aimless		data scaling
XDS		data reduction
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.11→45.031 Å / Cor.coef. F_o:F_c: 0.957 / Cor.coef. F_o:F_c free: 0.93 / SU B: 7.004 / SU ML: 0.095 / Cross valid method: FREE R-VALUE / ESU R: 0.154 / ESU R Free: 0.145
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2125	1313	4.773 %
R_work	0.1736	26196	-
all	0.175	-	-
obs	-	27509	99.982 %

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: 30.084 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.06 Å²	0.03 Å²	-0 Å²
2-	-	0.06 Å²	-0 Å²
3-	-	-	-0.193 Å²

Refinement step

Cycle: LAST / Resolution: 2.11→45.031 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	2387	0	54	173	2614

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.018	0.013	2551
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.015	2263
X-RAY DIFFRACTION	r_angle_refined_deg	2.15	1.681	3468
X-RAY DIFFRACTION	r_angle_other_deg	1.505	1.578	5204
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.972	5	305
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	34.255	22.782	133
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	16.321	15	407
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	17.308	15	13
X-RAY DIFFRACTION	r_chiral_restr	0.098	0.2	329
X-RAY DIFFRACTION	r_gen_planes_refined	0.013	0.02	2926
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	599
X-RAY DIFFRACTION	r_nbd_refined	0.19	0.2	439
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.201	0.2	2211
X-RAY DIFFRACTION	r_nbtor_refined	0.18	0.2	1194
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.091	0.2	1360
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.2	0.2	154
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.109	0.2	8
X-RAY DIFFRACTION	r_nbd_other	0.193	0.2	50
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.199	0.2	14
X-RAY DIFFRACTION	r_mcbond_it	2.016	1.919	1218
X-RAY DIFFRACTION	r_mcbond_other	2.018	1.913	1215
X-RAY DIFFRACTION	r_mcangle_it	3.333	2.858	1523
X-RAY DIFFRACTION	r_mcangle_other	3.333	2.858	1523
X-RAY DIFFRACTION	r_scbond_it	2.564	2.429	1333
X-RAY DIFFRACTION	r_scbond_other	2.563	2.43	1334
X-RAY DIFFRACTION	r_scangle_it	4.048	3.508	1945
X-RAY DIFFRACTION	r_scangle_other	4.047	3.51	1946
X-RAY DIFFRACTION	r_lrange_it	6.497	23.614	2749
X-RAY DIFFRACTION	r_lrange_other	6.455	23.354	2720

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
2.11-2.165	0.239	97	0.231	1888	X-RAY DIFFRACTION	100
2.165-2.224	0.271	102	0.22	1830	X-RAY DIFFRACTION	100
2.224-2.289	0.209	82	0.204	1797	X-RAY DIFFRACTION	100
2.289-2.359	0.224	82	0.179	1733	X-RAY DIFFRACTION	100
2.359-2.436	0.237	88	0.191	1703	X-RAY DIFFRACTION	99.9442
2.436-2.522	0.186	70	0.174	1653	X-RAY DIFFRACTION	100
2.522-2.617	0.218	76	0.174	1584	X-RAY DIFFRACTION	100
2.617-2.724	0.228	74	0.169	1550	X-RAY DIFFRACTION	100
2.724-2.845	0.221	94	0.164	1451	X-RAY DIFFRACTION	100
2.845-2.984	0.184	76	0.165	1394	X-RAY DIFFRACTION	100
2.984-3.145	0.22	68	0.16	1366	X-RAY DIFFRACTION	100
3.145-3.336	0.197	72	0.167	1264	X-RAY DIFFRACTION	100
3.336-3.566	0.198	60	0.17	1223	X-RAY DIFFRACTION	100
3.566-3.852	0.209	56	0.165	1131	X-RAY DIFFRACTION	100
3.852-4.22	0.196	41	0.153	1068	X-RAY DIFFRACTION	100
4.22-4.717	0.188	59	0.131	956	X-RAY DIFFRACTION	100
4.717-5.447	0.184	37	0.159	877	X-RAY DIFFRACTION	100
5.447-6.67	0.212	39	0.208	740	X-RAY DIFFRACTION	100
6.67-9.429	0.198	25	0.192	612	X-RAY DIFFRACTION	100
9.429-45.031	0.449	15	0.238	376	X-RAY DIFFRACTION	98.9873

Refinement TLS params.

Method: refined / Origin x: -14.8608 Å / Origin y: -31.8147 Å / Origin z: 11.5439 Å

	11	12	13	21	22	23	31	32	33
T	0.0691 Å²	-0.0052 Å²	0.0142 Å²	-	0.0057 Å²	-0.0037 Å²	-	-	0.0408 Å²
L	2.2546 °²	-0.4386 °²	0.2238 °²	-	0.9624 °²	0.2599 °²	-	-	1.0051 °²
S	0.0028 Å °	0.0696 Å °	-0.1651 Å °	-0.061 Å °	-0.0008 Å °	0.039 Å °	0.0542 Å °	-0.0421 Å °	-0.002 Å °

Refinement TLS group

Selection: ALL

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