7MEU

A biphenyl inhibitor of eIF4E targeting an internal binding site enables the design of cell-permeable PROTAC-degraders

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d7meub_	Alpha and beta proteins (a+b)	eIF4e-like	eIF4e-like	Translation initiation factor eIF4e	Translation initiation factor eIF4e	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d7meua_	Alpha and beta proteins (a+b)	eIF4e-like	eIF4e-like	Translation initiation factor eIF4e	Translation initiation factor eIF4e	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	eIF4e-like	8037387	3001871	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	eIF4e-like	8037387	3001871	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	IF4E	e7meuB1	A: a+b two layers	X: Translation initiation factor eIF4e and phosphothreonine lyase (From Topology)	H: Translation initiation factor eIF4e and phosphothreonine lyase (From Topology)	T: Translation initiation factor eIF4e and phosphothreonine lyase	F: IF4E	ECOD (1.6)
A	IF4E	e7meuA1	A: a+b two layers	X: Translation initiation factor eIF4e and phosphothreonine lyase (From Topology)	H: Translation initiation factor eIF4e and phosphothreonine lyase (From Topology)	T: Translation initiation factor eIF4e and phosphothreonine lyase	F: IF4E	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF01652	Eukaryotic initiation factor 4E (IF4E)	Eukaryotic initiation factor 4E	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Eukaryotic translation initiation factor 4E	translation regulator activity binding organic cyclic compound binding translation regulator activity, nucleic acid binding nucleic acid binding translation initiation factor activity translation factor activity, RNA binding protein binding translation initiation factor binding eukaryotic initiation factor 4G binding RNA binding mRNA cap binding RNA cap binding mRNA binding translation regulator activity binding organic cyclic compound binding translation regulator activity, nucleic acid binding nucleic acid binding translation initiation factor activity translation factor activity, RNA binding protein binding translation initiation factor binding eukaryotic initiation factor 4G binding RNA binding mRNA cap binding RNA cap binding mRNA binding RNA 7-methylguanosine cap binding transcription factor binding DNA-binding transcription factor binding enzyme binding	multicellular organismal process regulation of cellular process cellular developmental process regulation of developmental process negative regulation of biological process regulation of cell differentiation neurogenesis multicellular organism development neuron differentiation cell differentiation anatomical structure development negative regulation of cellular process negative regulation of cell differentiation system development multicellular organismal process regulation of cellular process cellular developmental process regulation of developmental process negative regulation of biological process regulation of cell differentiation neurogenesis multicellular organism development neuron differentiation cell differentiation anatomical structure development negative regulation of cellular process negative regulation of cell differentiation system development developmental process regulation of biological process negative regulation of developmental process biological regulation nervous system development generation of neurons cellular process negative regulation of neuron differentiation regulation of neuron differentiation biosynthetic process translational initiation metabolic process primary metabolic process protein metabolic process macromolecule metabolic process translation gene expression macromolecule biosynthetic process regulation of primary metabolic process post-transcriptional regulation of gene expression negative regulation of translation negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of protein metabolic process negative regulation of metabolic process regulation of macromolecule metabolic process regulation of gene expression negative regulation of gene expression negative regulation of biosynthetic process regulation of translation negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of metabolic process modulation of chemical synaptic transmission signaling regulation of translation at synapse, modulating synaptic transmission cell communication synaptic signaling postsynaptic modulation of chemical synaptic transmission trans-synaptic signaling regulation of signaling cell-cell signaling regulation of translation at postsynapse regulation of translation at synapse chemical synaptic transmission regulation of translation at postsynapse, modulating synaptic transmission regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of cell communication cellular localization nitrogen compound transport nucleocytoplasmic transport transport nuclear transport mRNA transport localization mRNA export from nucleus establishment of localization in cell RNA localization nuclear export nucleobase-containing compound transport RNA transport nucleic acid transport intracellular transport establishment of localization RNA export from nucleus establishment of RNA localization macromolecule localization cellular response to stimulus response to ketone response to lipid response to stimulus cellular response to endogenous stimulus response to hormone response to steroid hormone cellular response to ketone cellular response to steroid hormone stimulus response to organic cyclic compound cellular response to hormone stimulus response to endogenous stimulus cellular response to dexamethasone stimulus response to glucocorticoid cellular response to organic cyclic compound cellular response to glucocorticoid stimulus response to oxygen-containing compound cellular response to oxygen-containing compound cellular response to corticosteroid stimulus response to corticosteroid cellular response to chemical stimulus response to chemical cellular response to lipid response to dexamethasone maintenance of cell number stem cell population maintenance mitotic cell cycle process cell cycle phase transition cell cycle G1/S transition of mitotic cell cycle cell cycle G1/S phase transition mitotic cell cycle mitotic cell cycle phase transition cell cycle process behavioral defense response behavior fear response behavioral fear response defense response response to stress multicellular organismal response to stress positive regulation of biological process positive regulation of cell cycle regulation of mitotic cell cycle positive regulation of mitotic cell cycle regulation of cell cycle positive regulation of cellular process	protein-containing complex ribonucleoprotein complex RNAi effector complex RISC complex intracellular anatomical structure cytoplasmic ribonucleoprotein granule intracellular membraneless organelle ribonucleoprotein granule intracellular organelle cellular anatomical structure organelle membraneless organelle cytoplasm supramolecular complex protein-containing complex ribonucleoprotein complex RNAi effector complex RISC complex intracellular anatomical structure cytoplasmic ribonucleoprotein granule intracellular membraneless organelle ribonucleoprotein granule intracellular organelle cellular anatomical structure organelle membraneless organelle cytoplasm supramolecular complex cytoplasmic stress granule membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body nucleoplasm organelle lumen nuclear lumen extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space vesicle extracellular membrane-bounded organelle cytosol chromatoid body synapse cell junction glutamatergic synapse perinuclear region of cytoplasm P-body eukaryotic translation initiation factor 4F complex RNA cap binding complex intracellular protein-containing complex postsynapse

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR023398	Translation Initiation factor eIF- 4e-like	Homologous Superfamily
A, B	IPR019770	Eukaryotic translation initiation factor 4E (eIF-4E), conserved site	Conserved Site
A, B	IPR001040	Translation Initiation factor eIF- 4e	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P06730	Neoplasm Invasiveness mantle cell lymphoma ovarian cancer primitive neuroectodermal tumor tuberculosis astrocytic tumor autism spectrum disorder cancer large cell medulloblastoma lymphangioma malignant ependymoma oligodendroglioma pilocytic astrocytoma renal cell carcinoma tuberous sclerosis Neoplasm Invasiveness mantle cell lymphoma ovarian cancer primitive neuroectodermal tumor tuberculosis astrocytic tumor autism spectrum disorder cancer large cell medulloblastoma lymphangioma malignant ependymoma oligodendroglioma pilocytic astrocytoma renal cell carcinoma tuberous sclerosis atypical teratoid rhabdoid tumor autism, susceptibility to, 19 disappearing bone disease lung lymphangioleiomyomatosis malignant glioma medulloblastoma osteosarcoma subependymal giant cell astrocytoma autism glioblastoma

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.