PDB-8p9b: Crystal Structure of Mnk2-D228G in complex with Tinodasertib

ID or keywords:

Entry

Database: PDB / ID: 8p9b

Title

Crystal Structure of Mnk2-D228G in complex with Tinodasertib

Components

MAP kinase-interacting serine/threonine-protein kinase 2

Keywords

TRANSFERASE / MNK2 / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX

Function / homology

Function and homology information

calcium-dependent protein serine/threonine kinase activity / cellular response to arsenic-containing substance / calcium/calmodulin-dependent protein kinase activity / hemopoiesis / extrinsic apoptotic signaling pathway in absence of ligand / PML body / regulation of translation / calmodulin binding / cell surface receptor signaling pathway / protein phosphorylation ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.59 Å

Authors

Turnbull, A.P. / Sabin, V. / Bell, C. / Watson, M.

Funding support

United Kingdom, 1items

Citation

Journal: To Be Published
Title: Crystal Structure of Mnk2-D228G in complex with Tinodasertib
Authors: Sabin, V. / Turnbull, A.P. / Bell, C. / Watson, M.

History

Deposition	Jun 5, 2023	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Jun 12, 2024	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	8p9b.cif.gz	153 KB	Display	PDBx/mmCIF format
PDB format	pdb8p9b.ent.gz	92.5 KB	Display	PDB format
PDBx/mmJSON format	8p9b.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	8p9b_validation.pdf.gz	707.2 KB	Display	wwPDB validaton report
Full document	8p9b_full_validation.pdf.gz	708.5 KB	Display
Data in XML	8p9b_validation.xml.gz	11.7 KB	Display
Data in CIF	8p9b_validation.cif.gz	15 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/p9/8p9b ftp://data.pdbj.org/pub/pdb/validation_reports/p9/8p9b	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: MAP kinase-interacting serine/threonine-protein kinase 2

hetero molecules

36.1 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)	105.910, 105.910, 71.500
Angle α, β, γ (deg.)	90.000, 90.000, 120.000
Int Tables number	154
Space group name H-M	P3₂21

#1: Protein	MAP kinase-interacting serine/threonine-protein kinase 2 / MAP kinase signal-integrating kinase 2 / MAPK signal-integrating kinase 2 / Mnk2 Mass: 35604.461 Da / Num. of mol.: 1 / Mutation: D228G Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MKNK2, GPRK7, MNK2 / Production host: Escherichia coli (E. coli) References: UniProt: Q9HBH9, non-specific serine/threonine protein kinase
#2: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical	ChemComp-X8K / 4-[6-(4-morpholin-4-ylcarbonylphenyl)imidazo[1,2-a]pyridin-3-yl]benzenecarbonitrile Mass: 408.452 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₅H₂₀N₄O₂ / Feature type: SUBJECT OF INVESTIGATION
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: 3.79 Å³/Da / Density % sol: 67.59 %
Crystal grow	Temperature: 292 K / Method: vapor diffusion, sitting drop / pH: 8 Details: 24% (w/v) polyacrylic acid 5100, 2% (v/v) 2-Methyl-2,4-pentanediol, 100mM HEPES, pH 8.0

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å
Detector	Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jan 31, 2019
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9763 Å / Relative weight: 1
Reflection	Resolution: 2.59→56.39 Å / Num. obs: 14740 / % possible obs: 99.9 % / Redundancy: 9.6 % / CC_1/2: 1 / R_rim(I) all: 0.05 / Net I/σ(I): 24.4
Reflection shell	Resolution: 2.59→2.66 Å / Redundancy: 8.1 % / Mean I/σ(I) obs: 1.2 / Num. unique obs: 1099 / CC_1/2: 0.558 / R_rim(I) all: 1.617 / % possible all: 100

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0411	refinement
xia2		data reduction
Aimless		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.59→50.005 Å / Cor.coef. F_o:F_c: 0.953 / Cor.coef. F_o:F_c free: 0.938 / WR_factor R_free: 0.266 / WR_factor R_work: 0.209 / SU B: 21.773 / SU ML: 0.21 / Average fsc free: 0.9511 / Average fsc work: 0.969 / Cross valid method: FREE R-VALUE / ESU R: 0.326 / ESU R Free: 0.266
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.2636	738	5.013 %
R_work	0.2081	13983	-
all	0.211	-	-
obs	-	14721	99.932 %

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: 88.708 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.11 Å²	0.055 Å²	0 Å²
2-	-	0.11 Å²	-0 Å²
3-	-	-	-0.357 Å²

Refinement step

Cycle: LAST / Resolution: 2.59→50.005 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	2015	0	32	0	2047

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.007	0.012	2097
X-RAY DIFFRACTION	r_bond_other_d	0.002	0.016	1916
X-RAY DIFFRACTION	r_angle_refined_deg	1.358	1.662	2845
X-RAY DIFFRACTION	r_angle_other_deg	0.542	1.588	4386
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	7.074	5	260
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	6.976	5	9
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	16.464	10	314
X-RAY DIFFRACTION	r_dihedral_angle_other_3_deg	11.264	10	3
X-RAY DIFFRACTION	r_dihedral_angle_6_deg	15.095	10	90
X-RAY DIFFRACTION	r_chiral_restr	0.065	0.2	315
X-RAY DIFFRACTION	r_chiral_restr_other	1.188	0.2	4
X-RAY DIFFRACTION	r_gen_planes_refined	0.006	0.02	2429
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	477
X-RAY DIFFRACTION	r_nbd_refined	0.228	0.2	421
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.193	0.2	1800
X-RAY DIFFRACTION	r_nbtor_refined	0.185	0.2	1055
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.083	0.2	1164
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.124	0.2	40
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.251	0.2	9
X-RAY DIFFRACTION	r_nbd_other	0.188	0.2	58
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.161	0.2	6
X-RAY DIFFRACTION	r_mcbond_it	4.709	6.443	1049
X-RAY DIFFRACTION	r_mcbond_other	4.707	6.443	1049
X-RAY DIFFRACTION	r_mcangle_it	6.728	11.555	1306
X-RAY DIFFRACTION	r_mcangle_other	6.725	11.558	1307
X-RAY DIFFRACTION	r_scbond_it	6.245	6.61	1048
X-RAY DIFFRACTION	r_scbond_other	6.242	6.611	1049
X-RAY DIFFRACTION	r_scangle_it	8.579	12.052	1539
X-RAY DIFFRACTION	r_scangle_other	8.576	12.052	1540
X-RAY DIFFRACTION	r_lrange_it	9.667	62.017	2321
X-RAY DIFFRACTION	r_lrange_other	9.665	62.019	2322

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
2.59-2.658	0.388	41	0.365	1055	0.366	1096	0.952	0.94	100	0.354
2.658-2.73	0.546	41	0.314	989	0.322	1030	0.931	0.957	100	0.293
2.73-2.809	0.414	43	0.301	964	0.305	1007	0.918	0.959	100	0.27
2.809-2.895	0.361	50	0.296	934	0.3	984	0.941	0.958	100	0.259
2.895-2.99	0.323	44	0.23	929	0.234	974	0.949	0.971	99.8973	0.196
2.99-3.094	0.295	52	0.208	851	0.213	903	0.949	0.973	100	0.178
3.094-3.211	0.248	46	0.199	872	0.202	919	0.959	0.975	99.8912	0.17
3.211-3.341	0.304	58	0.208	797	0.214	855	0.95	0.974	100	0.186
3.341-3.489	0.277	49	0.195	777	0.199	826	0.95	0.978	100	0.176
3.489-3.659	0.284	33	0.201	779	0.205	812	0.957	0.977	100	0.186
3.659-3.855	0.263	27	0.2	728	0.202	757	0.959	0.979	99.7358	0.193
3.855-4.088	0.261	52	0.194	656	0.198	708	0.954	0.979	100	0.185
4.088-4.368	0.206	36	0.169	650	0.171	686	0.975	0.984	100	0.172
4.368-4.715	0.207	34	0.141	595	0.144	629	0.973	0.989	100	0.15
4.715-5.16	0.22	32	0.167	553	0.17	585	0.97	0.982	100	0.179
5.16-5.762	0.351	23	0.252	513	0.256	536	0.918	0.962	100	0.265
5.762-6.638	0.328	28	0.272	450	0.275	478	0.941	0.958	100	0.284
6.638-8.095	0.26	20	0.214	394	0.216	414	0.965	0.972	100	0.249
8.095-11.3	0.156	19	0.18	301	0.179	322	0.985	0.979	99.3789	0.217
11.3-50.005	0.322	10	0.267	196	0.27	206	0.951	0.946	100	0.317

Refinement TLS params.

Method: refined / Origin x: -10.8287 Å / Origin y: 73.9554 Å / Origin z: 2.7716 Å

	11	12	13	21	22	23	31	32	33
T	0.0585 Å²	0.0064 Å²	-0.0785 Å²	-	0.0811 Å²	-0.0731 Å²	-	-	0.206 Å²
L	4.2638 °²	0.7804 °²	1.3396 °²	-	3.3298 °²	1.3433 °²	-	-	2.5001 °²
S	-0.2038 Å °	-0.0606 Å °	0.6105 Å °	-0.172 Å °	-0.1502 Å °	0.1042 Å °	-0.3608 Å °	0.0819 Å °	0.3541 Å °

Refinement TLS group

Selection: ALL / Selection details: { A|71-531 }

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