7MEU: Eukaryotic translation initiation factor 4E

A biphenyl inhibitor of eIF4E targeting an internal binding site enables the design of cell-permeable PROTAC-degraders. Determined by X-ray diffraction at 1.91 Å resolution. Released 28 Apr 2021.

Method: X-ray diffraction
Resolution: 1.91 Å
Organism: Homo sapiens
Chains: 2
Atoms: 3,492
Mol. weight: 46.37 kDa
Ligands: MGP, Z5D
Released: 28 Apr 2021

Explore 7MEU in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7MEU contains 17 α-helices and 16 β-strands across 2 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 7 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	38-49	12	1
α-helix	56-59	4
β-strand	62-68	7	1
α-helix	69-82	14
β-strand	89-95	7	1
α-helix	105-108	4
β-strand	111-116	6	1
α-helix	123-138	16
α-helix	143-148	6
β-strand	149-155	7	1
β-strand	162-167	6	1
α-helix	173-186	14
β-strand	196-199	4	1
α-helix	200-204	5
β-strand	215-216	2	1

Chain B: 10 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	37	1
β-strand	38-49	12	2
α-helix	56-59	4
β-strand	60-68	9	2
α-helix	69-76	8
α-helix	82-84	3
α-helix	86	1
β-strand	89-95	7	2
β-strand	111-117	7	2
α-helix	119-138	20
α-helix	143-148	6
β-strand	149-156	8	2
β-strand	161-167	7	2
α-helix	173-187	15
β-strand	196-199	4	2
α-helix	200-204	5
α-helix	211-213	3
β-strand	215-216	2	2

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Eukaryotic translation initiation factor 4E	A, B	protein	192	Homo sapiens	P06730 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>7MEU_1 Eukaryotic translation initiation factor 4E (chains A, B)
MEVANPEHYIKHPLQNRWALWFFKNDKSKTWQANLRLISKFDTVEDFWALYNHIQLSSNL
MPGCDYSLFKDGIEPMWEDEKNKRGGRWLITLNKQQRRSDLDRFWLETLLCLIGESFDDY
SDDVCGAVVNVRAKGDKIAIWTTECENREAVTHIGRVYKERLGLPPKIVIGYQSHADTAT
KSGSTTKNRFVV

Ligands and cofactors

ID	Name	Formula	Copies
MGP	7-methyl-guanosine-5'-triphosphate	C11 H19 N5 O14 P3	2
Z5D	(2E)-2-{2-[4-([1,1'-biphenyl]-4-yl)-1,3-thiazol-2-yl]hydrazinylidene}-3-(2-nitr…	C24 H18 N4 O4 S	1

Primary citation

A biphenyl inhibitor of eIF4E targeting an internal binding site enables the design of cell-permeable PROTAC-degraders. Fischer, P.D., Papadopoulos, E., Dempersmier, J.M. et al. Eur J Med Chem (2021) 219:113435-113435. DOI 10.1016/j.ejmech.2021.113435 · PubMed

Other PDB entries of the same protein (UniProt P06730 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4TPW 1.5 Å, The co-complex structure of the translation initiation factor eIF4E with the inhibitor…
5T46 1.53 Å, Crystal structure of the human eIF4E-eIF4G complex
8QM8 1.58 Å, Potential drug binding sites for translation initiation factor eIF4E
4TQB 1.59 Å, The co-complex structure of the translation initiation factor eIF4E with the inhibitor…
5ZJY 1.59 Å, Stapled-peptides tailored against initiation of translation
7D6Y 1.67 Å, eIF4E in Complex with a Disulphide-Free Autonomous VH Domain
5ZJZ 1.67 Å, Stapled-peptides tailored against initiation of translation
5EI3 1.71 Å, Co-crystal structure of eIF4E with nucleotide mimetic inhibitor.
4UED 1.75 Å, Complex of human eIF4E with the 4E binding protein 4E-BP1
5ZK9 1.76 Å, Stapled-peptides tailored against initiation of translation
4TQC 1.8 Å, The co-complex structure of the translation initiation factor eIF4E with the inhibitor…
5ZML 1.8 Å, Stapled-peptides tailored against initiation of translation

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