PDB-8pon: TEAD2 in complex with an inhibitor

ID or keywords:

Entry

Database: PDB / ID: 8pon

Title

TEAD2 in complex with an inhibitor

Components

Transcriptional enhancer factor TEF-4

Keywords

SIGNALING PROTEIN / Inhibitor /

TEAD /

Complex

Function / homology

Function and homology information

TEAD-YAP complex / lateral mesoderm development / RUNX3 regulates YAP1-mediated transcription / notochord development / YAP1- and WWTR1 (TAZ)-stimulated gene expression / paraxial mesoderm development / hippo signaling /

regulation of stem cell differentiation / Formation of axial mesoderm / embryonic heart tube morphogenesis ...
Similarity search - Function

Biological species

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.2 Å

Authors

Guichou, J.F.

Funding support

France, 1items

Citation

Journal: Bioorg.Med.Chem.Lett. / Year: 2023
Title: Development of LM-41 and AF-2112, two flufenamic acid-derived TEAD inhibitors obtained through the replacement of the trifluoromethyl group by aryl rings.
Authors: Fnaiche, A. / Melin, L. / Suarez, N.G. / Paquin, A. / Vu, V. / Li, F. / Allali-Hassani, A. / Bolotokova, A. / Allemand, F. / Gelin, M. / Cotelle, P. / Woo, S. / LaPlante, S.R. / Barsyte- ...

History

Deposition	Jul 5, 2023	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Nov 22, 2023	Provider: repository / Type: Initial release

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	8pon.cif.gz	187.1 KB	Display	PDBx/mmCIF format
PDB format	pdb8pon.ent.gz	147.2 KB	Display	PDB format
PDBx/mmJSON format	8pon.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/po/8pon ftp://data.pdbj.org/pub/pdb/validation_reports/po/8pon	HTTPS FTP

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Related structure data

Related structure data	8p29C 8pojC 8pomC 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	#143 - Nov 2011 Toll-like Receptors similarity (1) #20 - Aug 2001 Poliovirus and Rhinovirus similarity (1) #258 - Jun 2021 Glucocorticoid Receptor and Dexamethasone similarity (1) #43 - Jul 2003 Src Tyrosine Kinase similarity (1)

Deposited unit

B: Transcriptional enhancer factor TEF-4

A: Transcriptional enhancer factor TEF-4

hetero molecules

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

1

B: Transcriptional enhancer factor TEF-4

hetero molecules

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

2

A: Transcriptional enhancer factor TEF-4

hetero molecules

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

Unit cell

Length a, b, c (Å)	80.117, 61.591, 111.292
Angle α, β, γ (deg.)	90.00, 102.57, 90.00
Int Tables number	5
Space group name H-M	I121

#1: Protein	Transcriptional enhancer factor TEF-4 / TEA domain family member 2 / TEAD-2 Mass: 27489.096 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TEAD2, TEF4 / Production host: Escherichia coli (E. coli) / References: UniProt: Q15562
#2: Chemical	ChemComp-MYR / MYRISTIC ACID / Myristic acid Mass: 228.371 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₁₄H₂₈O₂
#3: Chemical	ChemComp-ZUT / 4-fluoranyl-2-[(3-phenylmethoxyphenyl)amino]benzoic acid Mass: 337.344 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂₀H₁₆FNO₃ / Feature type: SUBJECT OF INVESTIGATION
#4: Water	ChemComp-HOH / water / Water Mass: 18.015 Da / Num. of mol.: 16 / 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: 2.82 Å³/Da / Density % sol: 56.31 %
Crystal grow	Temperature: 298 K / Method: vapor diffusion, hanging drop / Details: 2.8M sodium formate

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Type: ESRF BEAMLINE / Wavelength: 0.9697 Å
Detector	Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jun 10, 2023
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.9697 Å / Relative weight: 1
Reflection	Resolution: 2.2→53.58 Å / Num. obs: 26936 / % possible obs: 99.49 % / Redundancy: 2 % / CC_1/2: 0.996 / Net I/σ(I): 7.22
Reflection shell	Resolution: 2.2→2.28 Å / Num. unique obs: 2647 / CC_1/2: 0.598

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Processing

Software

Name	Version	Classification
PHENIX	(1.20.1_4487: ???)	refinement
XDS		data reduction
XDS		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.2→53.58 Å / SU ML: 0.32 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 32.83 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.2544	1333	4.95 %
R_work	0.2098	-	-
obs	0.212	26936	99.58 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL

Refinement step

Cycle: LAST / Resolution: 2.2→53.58 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	3323	0	40	16	3379

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.008	3453
X-RAY DIFFRACTION	f_angle_d	0.978	4662
X-RAY DIFFRACTION	f_dihedral_angle_d	9.407	468
X-RAY DIFFRACTION	f_chiral_restr	0.056	500
X-RAY DIFFRACTION	f_plane_restr	0.01	597

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 (%)
2.2-2.28	0.3939	136	0.3637	2542	X-RAY DIFFRACTION	100
2.28-2.37	0.3353	119	0.2984	2563	X-RAY DIFFRACTION	100
2.37-2.48	0.3033	131	0.2754	2521	X-RAY DIFFRACTION	100
2.48-2.61	0.3514	126	0.2924	2533	X-RAY DIFFRACTION	99
2.61-2.77	0.3131	135	0.2774	2554	X-RAY DIFFRACTION	99
2.77-2.99	0.3381	138	0.2639	2555	X-RAY DIFFRACTION	100
2.99-3.29	0.2693	142	0.2346	2541	X-RAY DIFFRACTION	100
3.29-3.76	0.2303	137	0.1864	2567	X-RAY DIFFRACTION	100
3.76-4.74	0.2105	120	0.1599	2612	X-RAY DIFFRACTION	100
4.74-53.58	0.2175	149	0.1832	2615	X-RAY DIFFRACTION	99

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	1.5302	0.6318	-2.7137	1.6383	0.9609	7.8966	-0.1979	-0.0461	-0.0369	0.2046	-0.2652	-0.0047	0.8232	-0.7291	0.3546	0.4609	-0.0453	0.0166	0.5751	-0.0587	0.324	-11.3083	-17.5955	39.665
2	5.9666	-0.1935	-0.1162	4.5093	-0.0034	4.6852	-0.2809	0.7973	-0.82	-0.2556	-0.1679	0.0024	0.7726	-1.0588	0.2389	0.4546	-0.0653	0.0678	0.4959	-0.1391	0.5598	-11.2631	-22.0083	25.9922
3	4.5627	0.5238	-1.4865	2.9894	-0.3401	5.9405	0.119	-0.8361	-0.2877	0.6868	-0.0667	-0.991	0.1495	1.9041	0.0586	0.6699	0.1092	-0.0703	1.0589	-0.0325	0.671	7.8385	-14.8792	46.2984
4	3.2486	1.4172	-0.7661	4.3083	0.1446	6.1839	0.3198	-0.1742	0.9621	0.2399	-0.0528	-0.858	-1.0462	1.7842	-0.2563	0.7207	-0.125	-0.0079	0.8427	-0.0699	0.623	2.8622	-4.5799	46.9952
5	4.403	-0.3358	-0.0947	2.7788	1.122	4.5079	0.0314	0.1351	-0.6195	0.1711	0.0326	-0.4928	0.7334	0.0046	-0.0329	0.3763	-0.0307	0.0836	0.2861	0.0126	0.4423	-1.6377	-18.6877	33.3402
6	0.8415	0.0774	-0.7024	1.9489	0.5946	4.1479	0.036	0.0147	-0.1669	0.1266	-0.1582	0.0055	-0.1715	-0.5953	0.08	0.4666	0.03	0.0313	0.544	0.0166	0.512	-10.1227	-9.123	36.3192
7	8.2972	2.8914	-2.6318	3.5795	-0.5526	3.9809	0.074	0.4565	0.6448	-0.6339	0.1839	0.2446	-0.157	-0.4838	-0.3339	0.5541	0.0912	0.0822	0.5155	0.1768	0.5311	-6.8614	-2.5521	34.097
8	5.0658	-1.0433	-2.7319	1.6031	1.4713	8.0124	0.0926	0.1577	-0.1253	0.3069	-0.1242	-0.1771	0.2893	-1.5047	0.0436	0.4012	-0.0106	-0.0628	0.9131	0.0685	0.4169	-19.652	-11.4604	35.2863
9	9.0095	-3.3643	-0.7754	8.2801	-0.0813	6.2945	0.0094	1.2919	0.3309	-0.79	0.1932	-0.4031	-0.0821	0.0794	-0.2251	0.3705	-0.0047	0.0588	0.4515	0.0256	0.4794	4.4847	-13.8804	19.7479
10	3.9621	-0.2173	-2.2088	1.1063	1.4333	4.2323	-0.0829	-0.2314	-0.0696	-0.0066	0.135	-0.2298	-0.1185	0.1419	0.0434	0.4679	0.0235	-0.0226	0.3249	0.0817	0.4079	0.1349	-12.1682	36.407
11	5.2986	0.0733	-0.6883	5.4993	1.6951	4.554	-0.2533	-0.1451	-0.7938	0.3133	0.4077	-0.5264	1.1567	0.2852	-0.0814	0.5374	0.0418	0.0465	0.3653	0.0572	0.509	0.4778	-24.2822	37.6205
12	6.8986	0.2997	0.2198	4.8071	-1.0078	3.7174	-0.3077	0.2137	1.5515	-0.0966	-0.0544	-0.2174	-0.1537	0.2287	0.0694	0.3753	0.0081	0.0555	0.4414	0.0696	0.479	-9.7212	19.4064	30.4558
13	7.5449	0.7856	-0.7554	3.5175	-1.8386	4.4307	-0.3441	0.3784	0.4085	-0.4092	0.2034	-0.0323	0.2862	-0.565	0.096	0.4832	-0.0368	0.0033	0.3465	0.062	0.5661	-6.128	13.821	24.6134
14	8.3879	0.5649	0.3196	0.9166	-0.1529	2.1281	-0.1515	-0.5241	0.0003	0.0076	0.1726	0.0631	0.0615	-0.2111	-0.0026	0.4399	0.0436	0.0171	0.3334	0.09	0.4163	-8.65	11.2487	32.2015
15	8.7019	-1.1207	-0.6635	3.889	-1.0353	6.7727	-1.0519	0.0939	2.1777	-0.4109	0.4901	0.5262	-1.9068	-0.375	0.3249	0.5737	-0.0262	-0.0244	0.4492	0.1655	0.9153	-4.0554	25.1426	26.7931

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'B' and (resid 219 through 238 )
2	X-RAY DIFFRACTION	2	chain 'B' and (resid 239 through 266 )
3	X-RAY DIFFRACTION	3	chain 'B' and (resid 267 through 277 )
4	X-RAY DIFFRACTION	4	chain 'B' and (resid 278 through 293 )
5	X-RAY DIFFRACTION	5	chain 'B' and (resid 294 through 325 )
6	X-RAY DIFFRACTION	6	chain 'B' and (resid 326 through 351 )
7	X-RAY DIFFRACTION	7	chain 'B' and (resid 352 through 362 )
8	X-RAY DIFFRACTION	8	chain 'B' and (resid 363 through 380 )
9	X-RAY DIFFRACTION	9	chain 'B' and (resid 381 through 395 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 396 through 430 )
11	X-RAY DIFFRACTION	11	chain 'B' and (resid 431 through 446 )
12	X-RAY DIFFRACTION	12	chain 'A' and (resid 222 through 277 )
13	X-RAY DIFFRACTION	13	chain 'A' and (resid 278 through 325 )
14	X-RAY DIFFRACTION	14	chain 'A' and (resid 326 through 430 )
15	X-RAY DIFFRACTION	15	chain 'A' and (resid 431 through 446 )

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