PDB-3enm: The structure of the MAP2K MEK6 reveals an autoinhibitory dimer

ID or keywords:

Entry

Database: PDB / ID: 3enm

Title

The structure of the MAP2K MEK6 reveals an autoinhibitory dimer

Components

Dual specificity mitogen-activated protein kinase kinase 6

Keywords

TRANSFERASE / MEK6 / autoinhibited dimer / ATP-binding / Kinase / Nucleotide-binding / Phosphoprotein / Serine/threonine-protein kinase / Tyrosine-protein kinase

Function / homology

Function and homology information

cellular response to sorbitol / ovulation cycle process / nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / positive regulation of prostaglandin secretion / mitogen-activated protein kinase kinase / stress-activated protein kinase signaling cascade / negative regulation of cold-induced thermogenesis / Myogenesis / positive regulation of nitric-oxide synthase biosynthetic process / PI5P Regulates TP53 Acetylation ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

SAD / Resolution: 2.35 Å

Authors

Min, X. / Akella, R. / He, H. / Humphreys, J.M. / Tsutakawa, S. / Lee, S.-J. / Tainer, J.A. / Cobb, M.H. / Goldsmith, E.J.

Citation

Journal: Structure / Year: 2009
Title: The structure of the MAP2K MEK6 reveals an autoinhibitory dimer
Authors: Min, X. / Akella, R. / He, H. / Humphreys, J.M. / Tsutakawa, S.E. / Lee, S.J. / Tainer, J.A. / Cobb, M.H. / Goldsmith, E.J.

History

Deposition	Sep 25, 2008	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Mar 3, 2009	Provider: repository / Type: Initial release
Revision 1.1	Jul 13, 2011	Group: Advisory / Version format compliance
Revision 1.2	Oct 20, 2021	Group: Database references / Derived calculations ...Database references / Derived calculations / Source and taxonomy / Structure summary Category: database_2 / entity ...database_2 / entity / entity_src_gen / entity_src_nat / struct_conn / struct_ref_seq_dif / struct_site Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity.src_method / _struct_conn.pdbx_leaving_atom_flag / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	3enm.cif.gz	233.2 KB	Display	PDBx/mmCIF format
PDB format	pdb3enm.ent.gz	198.4 KB	Display	PDB format
PDBx/mmJSON format	3enm.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	3enm_validation.pdf.gz	509.3 KB	Display	wwPDB validaton report
Full document	3enm_full_validation.pdf.gz	568.7 KB	Display
Data in XML	3enm_validation.xml.gz	49.9 KB	Display
Data in CIF	3enm_validation.cif.gz	68.9 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/en/3enm ftp://data.pdbj.org/pub/pdb/validation_reports/en/3enm	HTTPS FTP

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Related structure data

Similar structure data	4du5-2 2awd-d 2fpe-7 5c3y-4 2wcf-d 6wgz-1 3uyt-6 5c3y-3 1c1d-1 3ljs-1 Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) Search similar-shape structures by Omokage search (details) 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	#28 - Apr 2002 Anthrax Toxin similarity (2) #195 - Mar 2016 RAF Protein Kinases similarity (2) #31 - Jul 2002 p53 Tumor Suppressor similarity (1) #122 - Feb 2010 Enhanceosome similarity (1) #213 - Sep 2017 Sirtuins similarity (1) #44 - Aug 2003 Calmodulin similarity (1) #43 - Jul 2003 Src Tyrosine Kinase similarity (1) #221 - May 2018 Human Papillomavirus and Vaccines similarity (1) #234 - Jun 2019 MDM2 and Cancer similarity (1) #196 - Apr 2016 Lead Poisoning similarity (1)

PDB pages

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Related items in Molecule of the Month

#28 - Apr 2002
Anthrax Toxin
similarity (2)
#195 - Mar 2016
RAF Protein Kinases
similarity (2)
#31 - Jul 2002
p53 Tumor Suppressor
similarity (1)
#122 - Feb 2010
Enhanceosome
similarity (1)
#213 - Sep 2017
Sirtuins
similarity (1)
#44 - Aug 2003
Calmodulin
similarity (1)
#43 - Jul 2003
Src Tyrosine Kinase
similarity (1)
#221 - May 2018
Human Papillomavirus and Vaccines
similarity (1)
#234 - Jun 2019
MDM2 and Cancer
similarity (1)
#196 - Apr 2016
Lead Poisoning
similarity (1)

Deposited unit

A: Dual specificity mitogen-activated protein kinase kinase 6

B: Dual specificity mitogen-activated protein kinase kinase 6

C: Dual specificity mitogen-activated protein kinase kinase 6

D: Dual specificity mitogen-activated protein kinase kinase 6

hetero molecules

147 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Dual specificity mitogen-activated protein kinase kinase 6

C: Dual specificity mitogen-activated protein kinase kinase 6

hetero molecules

defined by author&software
73.6 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Dual specificity mitogen-activated protein kinase kinase 6

hetero molecules

D: Dual specificity mitogen-activated protein kinase kinase 6

hetero molecules

defined by author&software
73.6 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	122.663, 122.663, 195.540
Angle α, β, γ (deg.)	90.00, 90.00, 120.00
Int Tables number	154
Space group name H-M	P3₂21

#1: Protein	Dual specificity mitogen-activated protein kinase kinase 6 / MAP kinase kinase 6 / MAPKK 6 / MAPK/ERK kinase 6 / SAPKK3 Mass: 36664.062 Da / Num. of mol.: 4 / Fragment: residues 45-334 / Mutation: S207D T211D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) References: UniProt: P52564, mitogen-activated protein kinase kinase
#2: Chemical	ChemComp-SO4 / SULFATE ION Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO₄
#3: Chemical	ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₃H₈O₃
#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.: 325 / Source method: isolated from a natural source / Formula: H₂O

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Experiment

Experiment	Method: X-RAY DIFFRACTION

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Sample preparation

Crystal	Density Matthews: 2.9 Å³/Da / Density % sol: 57.52 %
Crystal grow	Temperature: 289 K / Method: vapor diffusion, hanging drop / pH: 8 Details: 1.6M Li2SO4 0.1M Tris-HCl, pH 8.0, VAPOR DIFFUSION, HANGING DROP, temperature 289K

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 19-BM / Wavelength: 0.97905 Å
Detector	Type: CUSTOM-MADE / Detector: CCD / Date: Oct 1, 2005
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.97905 Å / Relative weight: 1
Reflection	Resolution: 2.3→50 Å / Num. all: 71583 / Num. obs: 71326 / Redundancy: 3.4 % / R_sym value: 0.07

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Processing

Software

Name	Version	Classification
HKL-2000		data collection
SHELXS		phasing
REFMAC	5.3.0040	refinement
HKL-2000		data reduction
HKL-2000		data scaling

Refinement

Method to determine structure:

SAD / Resolution: 2.35→19.97 Å / Cor.coef. F_o:F_c: 0.948 / Cor.coef. F_o:F_c free: 0.92 / SU B: 17.714 / SU ML: 0.187 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.277 / ESU R Free: 0.238 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.26886	3582	5.1 %	RANDOM
R_work	0.21199	-	-	-
obs	0.21485	67293	99.35 %	-

Solvent computation

Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK

Displacement parameters

B_iso mean: 58.13 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	0.16 Å²	0.08 Å²	0 Å²
2-	-	0.16 Å²	0 Å²
3-	-	-	-0.23 Å²

Refinement step

Cycle: LAST / Resolution: 2.35→19.97 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	8814	0	30	325	9169

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.019	0.022	8999
X-RAY DIFFRACTION	r_bond_other_d
X-RAY DIFFRACTION	r_angle_refined_deg	1.948	1.979	12154
X-RAY DIFFRACTION	r_angle_other_deg
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.913	5	1098
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	35.615	24.637	386
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	20.216	15	1658
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	22.23	15	44
X-RAY DIFFRACTION	r_chiral_restr	0.135	0.2	1367
X-RAY DIFFRACTION	r_gen_planes_refined	0.009	0.021	6624
X-RAY DIFFRACTION	r_gen_planes_other
X-RAY DIFFRACTION	r_nbd_refined	0.229	0.2	4389
X-RAY DIFFRACTION	r_nbd_other
X-RAY DIFFRACTION	r_nbtor_refined	0.309	0.2	6247
X-RAY DIFFRACTION	r_nbtor_other
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.18	0.2	465
X-RAY DIFFRACTION	r_xyhbond_nbd_other
X-RAY DIFFRACTION	r_metal_ion_refined
X-RAY DIFFRACTION	r_metal_ion_other
X-RAY DIFFRACTION	r_symmetry_vdw_refined	0.215	0.2	118
X-RAY DIFFRACTION	r_symmetry_vdw_other
X-RAY DIFFRACTION	r_symmetry_hbond_refined	0.208	0.2	37
X-RAY DIFFRACTION	r_symmetry_hbond_other
X-RAY DIFFRACTION	r_symmetry_metal_ion_refined
X-RAY DIFFRACTION	r_symmetry_metal_ion_other
X-RAY DIFFRACTION	r_mcbond_it	0.826	1.5	5530
X-RAY DIFFRACTION	r_mcbond_other
X-RAY DIFFRACTION	r_mcangle_it	1.537	2	8995
X-RAY DIFFRACTION	r_scbond_it	2.647	3	3469
X-RAY DIFFRACTION	r_scangle_it	4.103	4.5	3158
X-RAY DIFFRACTION	r_rigid_bond_restr
X-RAY DIFFRACTION	r_sphericity_free
X-RAY DIFFRACTION	r_sphericity_bonded

LS refinement shell

Resolution: 2.35→2.41 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.344	253	-
R_work	0.302	4923	-
obs	-	-	99.48 %

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	2.2756	1.0955	4.6008	1.8695	2.8277	9.5813	0.0445	0.5034	-0.4783	-0.1855	0.2483	0.0164	0.9412	0.4334	-0.2928	-0.0256	-0.0093	0.1398	0.1284	0.1131	0.1134	-1.229	26.86	23.773
2	1.88	-0.4737	-1.8643	2.3518	0.1082	4.083	-0.0891	0.1016	-0.3506	-0.054	-0.0812	0.2849	0.4406	-0.1354	0.1703	-0.237	0.022	0.0207	-0.0406	-0.0157	-0.2053	-3.739	36.088	11.555
3	2.3076	-0.0117	-0.4351	3.7016	-0.5356	2.3926	0.0868	0.0177	0.0633	-0.1886	-0.0919	0.5448	0.0145	-0.3272	0.0051	-0.2603	0.039	0.0172	0.0384	-0.0611	-0.2002	-7.086	45.057	-0.483
4	2.6647	-1.4991	-0.6907	3.3791	0.1483	1.5861	0.1341	0.262	0.2156	-0.4438	-0.0592	-0.177	-0.114	0.1637	-0.0748	-0.1847	0.0482	0.073	0.0351	0.009	-0.2549	2.884	49.625	-7.154
5	8.9472	-0.8111	-8.0558	2.4841	2.771	8.9809	2.0644	0.056	2.296	1.5461	-0.858	-1.0939	0.137	0.3061	-1.2064	0.618	0.0495	-0.0021	0.508	0.1703	0.4919	-11.931	57.868	48.554
6	1.5465	2.0259	1.8052	7.5999	1.2213	2.3716	0.0689	-0.5331	0.1798	0.8531	-0.26	-0.1807	-0.381	0.2319	0.191	-0.0683	0.0799	-0.1312	-0.0091	0.0198	-0.0337	-15.819	58.462	38.844
7	1.3345	-0.7083	0.0358	5.9971	-0.5504	2.7279	-0.0721	-0.1851	0.1453	0.4302	0.1099	-1.0939	-0.0767	0.5195	-0.0377	-0.2441	-0.0269	-0.0784	-0.0569	-0.0432	0.0024	-12.279	72.418	31.81
8	2.8367	-0.8789	-1.1997	2.2448	0.9823	4.7275	0.2447	0.108	0.3461	-0.2387	0.0113	-0.5184	-0.4562	0.257	-0.256	-0.2442	-0.0289	0.0337	-0.2215	0.0249	0.0007	-14.248	79.609	19.48
9	2.0496	-1.0608	0.9835	1.6754	0.6731	14.4563	0.0878	0.0057	-0.0565	0.385	-0.1173	0.0147	-0.1151	-0.3338	0.0296	0.024	-0.0207	-0.0162	0.1549	0.0397	0.1586	11.683	49.429	25.811
10	0.5508	-0.4029	1.7959	0.2948	-1.3138	5.8554	1.6267	-0.7567	-0.731	2.1341	-0.4046	-1.9894	0.5215	0.8814	-1.2222	0.3696	0.0534	0.1672	0.5004	-0.1078	0.5714	9.943	34.689	15.362
11	3.7014	-1.258	1.5746	1.1773	-1.4365	3.9554	-0.3497	-0.0701	0.3944	0.1979	0.1067	-0.1127	-0.3455	0.2554	0.2429	-0.2814	0.0464	0.0334	0.0086	0.0301	-0.0692	9.589	34.828	37.737
12	5.4182	-0.275	-1.9187	2.6713	0.5367	2.8215	-0.1368	-0.2957	-0.5352	0.3408	0.0677	-0.0241	0.4225	0.2646	0.069	-0.0439	0.1992	0.1047	-0.0646	0.1258	-0.0726	6.983	19.828	50.383
13	8.0544	-6.373	-1.9632	9.4672	2.3399	0.7524	-0.115	-0.2176	-0.4276	-0.3412	-0.1172	0.9154	-0.222	-0.7316	0.2323	-0.0036	-0.061	0.0181	0.1528	0.1065	-0.0296	33.31	49.475	37.395
14	4.854	0.124	0.5522	2.3317	-0.2531	3.0114	-0.1093	-0.3887	0.1808	0.2796	0.1023	0.3606	-0.1542	-0.6144	0.0071	-0.2941	-0.0199	-0.0531	0.1658	0.0696	-0.1038	32.932	62.112	34.449
15	2.5904	0.3037	0.0612	2.7867	-0.5075	3.6167	-0.1113	-0.2858	0.1278	-0.0962	0.1377	0.2383	0.0325	-0.2075	-0.0263	-0.275	-0.0093	-0.1315	0.0645	0.1294	-0.0676	27.947	65.667	18.354
16	3.6483	1.0718	-0.6985	1.9572	-0.6629	2.362	-0.1251	-0.0081	0.3415	-0.0817	0.0781	0.3732	-0.3008	-0.3462	0.0471	-0.1255	0.0282	-0.2112	0.0001	0.1123	-0.0874	29.217	75.321	9.08

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Auth asym-ID	Auth seq-ID
1	X-RAY DIFFRACTION	1	A	46 - 65
2	X-RAY DIFFRACTION	2	A	66 - 154
3	X-RAY DIFFRACTION	3	A	155 - 241
4	X-RAY DIFFRACTION	4	A	242 - 333
5	X-RAY DIFFRACTION	5	B	49 - 57
6	X-RAY DIFFRACTION	6	B	58 - 93
7	X-RAY DIFFRACTION	7	B	94 - 183
8	X-RAY DIFFRACTION	8	B	184 - 332
9	X-RAY DIFFRACTION	9	C	48 - 56
10	X-RAY DIFFRACTION	10	C	57 - 62
11	X-RAY DIFFRACTION	11	C	63 - 205
12	X-RAY DIFFRACTION	12	C	206 - 333
13	X-RAY DIFFRACTION	13	D	43 - 65
14	X-RAY DIFFRACTION	14	D	66 - 129
15	X-RAY DIFFRACTION	15	D	130 - 220
16	X-RAY DIFFRACTION	16	D	221 - 333

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