8qng

Crystal structure of the E3 ubiquitin ligase Cbl-b with an allosteric inhibitor (benzodiazepine HTS hit compound 1)

Method: X-RAY DIFFRACTION D_max: 70.8 Å Quality: EXCELLENT

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1. Protein Identity and Related Structures Protein Identity & Related Structures

E3 ubiquitin-protein ligase CBL-B

Homo sapiens

State in the Current Structure

Assembly	Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Associated Components	Method and Experimental Conditions	Structure Quality
1	Protein monomer Monomer Protein × 1 PDB declaration: monomeric（1） Consistent with protein copy count	Chain A； UniProt 36–427	Not recorded	W89 2-(morpholin-4-ylmethyl)-~{N}-[(3~{S})-2-oxidanylidene-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]benzamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions：VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；9 % PEG8000, 0.05 M MgAcetate, 0.05 M PCTP pH 7.5	Resolution 2.20 Å R-free 0.295

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

Other PDB	Difference from Current Entry 8QNG	Assembly / Oligomeric State	Construct	Mutations and Modifications	Ligands, Ions and Non-polymers	Method and Experimental Conditions	Structure Quality
2AK5 beta PIX-SH3 complexed with a Cbl-b peptide Deposited 2005-08-03	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 6 PDB declaration: hexameric	Chain D 904–911（8 aa） Fragment：residues 904-911	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions pH 6.5；291 K；PEG 3000, SODIUM CITRATE, pH 6.5, VAPOR DIFFUSION, SITTING DROP, temperature 291K, pH 6.50	Resolution 1.85 Å R-free 0.269
2BZ8 N-terminal Sh3 domain of CIN85 bound to Cbl-b peptide Deposited 2005-08-12	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 3 PDB declaration: trimeric	Chain C 902–912（11 aa） Fragment：POLYPROLINE RICH REGION RESIDUES 902-912	Not recorded	NA SODIUM ION × 2	X-RAY DIFFRACTION X-ray crystallization conditions pH 7.5；0.8 M NA CITRATE, 0.1 M BIS-TRIS PH 7.5, 0.2 M NACL	Resolution 2.00 Å R-free 0.271
2DO6 Solution structure of RSGI RUH-065, a UBA domain from human cDNA Deposited 2006-04-27	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein homooligomer Homooligomer；Protein × 2 PDB declaration: dimeric	Chain A 931–970（40 aa） Fragment：UBA domain Chain B 931–970（40 aa） Fragment：UBA domain	Not recorded	No recorded non-water small molecule	SOLUTION NMR NMR measurement conditions pH 7；298 K；Ionic strength (raw mmCIF value) 100mM NaCl；Pressure AMBIENT NMR sample composition 1.1mM UBA domain U-15N,13C, 20mM d-Tris-HCl buffer (pH 7.0), 100mM NaCl, 1mM d-DTT, 0.02% NaN3, 90% H2O, 10% D2O \| 90% H2O/10% D2O NMR sample composition 1.0mM UBA domain U-15N,13C, 1.0mM UBA domain, 20mM d-Tris-HCl buffer (pH 7.0), 100mM NaCl, 1mM d-DTT, 0.02% NaN3, 100% D2O \| 100% D2O	Resolution not provided
2J6F N-TERMINAL SH3 DOMAIN OF CMS (CD2AP HUMAN HOMOLOG) BOUND TO CBL-B PEPTIDE Deposited 2006-09-28	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain C 902–912（11 aa） Fragment：PEPTIDE, RESIDUES 902-912	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions pH 5.5；20% PEG3000, 0.1M ACETATE PH 5.5	Resolution 1.70 Å R-free 0.218
2JNH Solution Structure of the UBA Domain from Cbl-b Deposited 2007-01-24	Different construct Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 926–971（46 aa） Fragment：UBA domain	Not recorded	No recorded non-water small molecule	SOLUTION NMR NMR measurement conditions pH 6.5；298 K；Pressure ambient NMR sample composition 1 mM [U-13C; U-15N] entity, 20 mM sodium phosphate, 50 mM sodium chloride, 1 mM DTT, 0.01 % sodium azide, 90% H2O/10% D2O \| 90% H2O/10% D2O	Resolution not provided
2LDR Solution structure of Helix-RING domain of Cbl-b in the Tyr363 phosphorylated form Deposited 2011-06-01	Different construct Different mutation/modification Different ligand/ion Different experimental method Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 351–426（76 aa） Fragment：Helix-RING domain, residues 345-426	Non-standard monomer：Yes (specific site not provided by mmCIF)	ZN ZINC ION × 2	SOLUTION NMR NMR measurement conditions pH 6.3；298 K；Ionic strength (raw mmCIF value) 150；Pressure ambient NMR sample composition 20mM MES-1, 2mM DTT-2, 150mM sodium chloride-3, 0.4mM [U-99% 13C; U-99% 15N] protein-4, 90% H2O/10% D2O \| 90% H2O/10% D2O	Resolution not provided
2OOA crystal structure of the UBA domain from Cbl-b ubiquitin ligase Deposited 2007-01-25	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 924–973（50 aa） Fragment：UBA domain	Non-standard monomer：Yes (specific site not provided by mmCIF)	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 8.2；293 K；1.2M sodium/potassium phosphate, 12% glycerol, pH 8.2, VAPOR DIFFUSION, HANGING DROP, temperature 293K	Resolution 1.56 Å R-free 0.240
2OOA crystal structure of the UBA domain from Cbl-b ubiquitin ligase Deposited 2007-01-25	Different construct Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain B 924–973（50 aa） Fragment：UBA domain	Non-standard monomer：Yes (specific site not provided by mmCIF)	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 8.2；293 K；1.2M sodium/potassium phosphate, 12% glycerol, pH 8.2, VAPOR DIFFUSION, HANGING DROP, temperature 293K	Resolution 1.56 Å R-free 0.240
2OOB crystal structure of the UBA domain from Cbl-b ubiquitin ligase in complex with ubiquitin Deposited 2007-01-25	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 924–973（50 aa） Fragment：UBA domain	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；pH 5；293 K；0.2M calcium chloride, 0.1M sodium acetate, 20% PEG6000, pH 5.0, VAPOR DIFFUSION, HANGING DROP, temperature 293K	Resolution 1.90 Å R-free 0.256
3PFV Crystal structure of Cbl-b TKB domain in complex with EGFR pY1069 peptide Deposited 2010-10-29	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain A 38–344（307 aa） Fragment：N-terminal TKB domain (UNP residues 38-344)	Not recorded	NA SODIUM ION × 1 CL CHLORIDE ION × 2 SO4 SULFATE ION × 4 EDO 1,2-ETHANEDIOL × 3	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 6.5；293.15 K；30% PEG 3350, 0.3M Ammonium sulfate, 0.1M Bis-Tris, pH 6.5, VAPOR DIFFUSION, SITTING DROP, temperature 293.15K	Resolution 2.27 Å R-free 0.262
3PFV Crystal structure of Cbl-b TKB domain in complex with EGFR pY1069 peptide Deposited 2010-10-29	Different construct Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein heterocomplex Heteromer；Protein × 2 PDB declaration: dimeric	Chain B 38–344（307 aa） Fragment：N-terminal TKB domain (UNP residues 38-344)	Not recorded	NA SODIUM ION × 1 SO4 SULFATE ION × 3 PG4 TETRAETHYLENE GLYCOL × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 6.5；293.15 K；30% PEG 3350, 0.3M Ammonium sulfate, 0.1M Bis-Tris, pH 6.5, VAPOR DIFFUSION, SITTING DROP, temperature 293.15K	Resolution 2.27 Å R-free 0.262
3VGO Crystal structure of the N-terminal fragment of Cbl-b Deposited 2011-08-18	Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 39–426（388 aa） Fragment：N-terminal fragment, UNP residues 39-426	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8.4；293 K；25% PEG 3350, 0.1M bicine, 0.8M KNO3, pH 8.4, VAPOR DIFFUSION, SITTING DROP, temperature 293K	Resolution 3.10 Å R-free 0.328
3VGO Crystal structure of the N-terminal fragment of Cbl-b Deposited 2011-08-18	Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain B 39–426（388 aa） Fragment：N-terminal fragment, UNP residues 39-426	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8.4；293 K；25% PEG 3350, 0.1M bicine, 0.8M KNO3, pH 8.4, VAPOR DIFFUSION, SITTING DROP, temperature 293K	Resolution 3.10 Å R-free 0.328
3VGO Crystal structure of the N-terminal fragment of Cbl-b Deposited 2011-08-18	Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 3 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain C 39–426（388 aa） Fragment：N-terminal fragment, UNP residues 39-426	Not recorded	No recorded non-water small molecule	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8.4；293 K；25% PEG 3350, 0.1M bicine, 0.8M KNO3, pH 8.4, VAPOR DIFFUSION, SITTING DROP, temperature 293K	Resolution 3.10 Å R-free 0.328
3ZNI Structure of phosphoTyr363-Cbl-b - UbcH5B-Ub - ZAP-70 peptide complex Deposited 2013-02-14	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain A 36–427（392 aa） Fragment：RESIDUES 36-427	Mutation：YES Non-standard monomer：Yes (specific site not provided by mmCIF)	ZN ZINC ION × 2 CA CALCIUM ION × 1 EDO 1,2-ETHANEDIOL × 1	X-RAY DIFFRACTION X-ray crystallization conditions 0.1 M BICINE, PH 9.0, 8-11% (W/V) PEG 3350 AND 0.1 M SODIUM FORMATE	Resolution 2.21 Å R-free 0.211
3ZNI Structure of phosphoTyr363-Cbl-b - UbcH5B-Ub - ZAP-70 peptide complex Deposited 2013-02-14	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain E 36–427（392 aa） Fragment：RESIDUES 36-427	Mutation：YES Non-standard monomer：Yes (specific site not provided by mmCIF)	ZN ZINC ION × 2 CA CALCIUM ION × 1 EDO 1,2-ETHANEDIOL × 1	X-RAY DIFFRACTION X-ray crystallization conditions 0.1 M BICINE, PH 9.0, 8-11% (W/V) PEG 3350 AND 0.1 M SODIUM FORMATE	Resolution 2.21 Å R-free 0.211
3ZNI Structure of phosphoTyr363-Cbl-b - UbcH5B-Ub - ZAP-70 peptide complex Deposited 2013-02-14	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 3 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain I 36–427（392 aa） Fragment：RESIDUES 36-427	Mutation：YES Non-standard monomer：Yes (specific site not provided by mmCIF)	ZN ZINC ION × 2 CA CALCIUM ION × 1 EDO 1,2-ETHANEDIOL × 1	X-RAY DIFFRACTION X-ray crystallization conditions 0.1 M BICINE, PH 9.0, 8-11% (W/V) PEG 3350 AND 0.1 M SODIUM FORMATE	Resolution 2.21 Å R-free 0.211
3ZNI Structure of phosphoTyr363-Cbl-b - UbcH5B-Ub - ZAP-70 peptide complex Deposited 2013-02-14	Different construct Different mutation/modification Different oligomeric state Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 4 Protein heterocomplex Heteromer；Protein × 4 PDB declaration: tetrameric	Chain M 36–427（392 aa） Fragment：RESIDUES 36-427	Mutation：YES Non-standard monomer：Yes (specific site not provided by mmCIF)	ZN ZINC ION × 2 CA CALCIUM ION × 1 EDO 1,2-ETHANEDIOL × 1	X-RAY DIFFRACTION X-ray crystallization conditions 0.1 M BICINE, PH 9.0, 8-11% (W/V) PEG 3350 AND 0.1 M SODIUM FORMATE	Resolution 2.21 Å R-free 0.211
8GCY Co-crystal structure of CBL-B in complex with N-Aryl isoindolin-1-one inhibitor Deposited 2023-03-03	Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 38–427（390 aa）	Not recorded	ZN ZINC ION × 2 Z3N 2-{3-[(1s,3R)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl]phenyl}-6-{[(3S)-3-methylpiperidin-1-yl]methyl}-4-(trifluoromethyl)-2,3-dihydro-1H-isoindol-1-one × 1 EDO 1,2-ETHANEDIOL × 1 SO4 SULFATE ION × 1 UNX UNKNOWN LIGAND × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 6.5；291 K；0.1 M Imidazole, 0.1 M MES monohydrate pH 6.5 0.09 M Sodium nitrate, 0.09 M Sodium phosphate dibasic, 0.09M Ammonium sulfate 12.5% v/v MPD; 12.5% PEG1000; 12.5% w/v PEG 3350	Resolution 1.81 Å R-free 0.230
8QNH Crystal structure of the E3 ubiquitin ligase Cbl-b with an allosteric inhibitor (WO2020264398 Ex23) Deposited 2023-09-26	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–427（392 aa）	Not recorded	Z3N 2-{3-[(1s,3R)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl]phenyl}-6-{[(3S)-3-methylpiperidin-1-yl]methyl}-4-(trifluoromethyl)-2,3-dihydro-1H-isoindol-1-one × 1 ZN ZINC ION × 2 NA SODIUM ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；9 % PEG8000, 5 % MPD, 0.05 M MgAcetate, 0.05 M PCTP pH 8	Resolution 2.00 Å R-free 0.248
8QNI Crystal structure of the E3 ubiquitin ligase Cbl-b with an allosteric inhibitor (benzodiazepine compound 25) Deposited 2023-09-26	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–427（392 aa）	Not recorded	W7R 2-[[(2~{S})-2-methylmorpholin-4-yl]methyl]-~{N}-[(3~{S})-2-oxidanylidene-5-phenyl-1,3-dihydropyrido[3,4-e][1,4]diazepin-3-yl]benzamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；11 % PEG8000, 5 % MPD, 0.05 M MgAcetate, 0.05 M PCPT pH 8.0	Resolution 2.48 Å R-free 0.286
8QTG Crystal structure of CBL-b in complex with an allosteric inhibitor (compound 9) Deposited 2023-10-12	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–427（392 aa）	Not recorded	WUQ 3-[3-[3-methyl-1-(4-methyl-1,2,4-triazol-3-yl)cyclobutyl]phenyl]-5-(trifluoromethyl)-1~{H}-pyridin-2-one × 1 ZN ZINC ION × 2 NA SODIUM ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；8-11 % PEG8000, 5 % MPD, 0.05 M MgAcetate, 0.05 M PCTP pH 8	Resolution 1.42 Å R-free 0.243
8QTH Crystal structure of CBL-b in complex with an allosteric inhibitor (compound 8) Deposited 2023-10-12	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–427（392 aa）	Not recorded	WX0 1-methyl-5-[3-[3-methyl-1-(4-methyl-1,2,4-triazol-3-yl)cyclobutyl]phenyl]-3-(trifluoromethyl)-7H-pyrrolo[2,3-b]pyridin-6-one × 1 ZN ZINC ION × 2 NA SODIUM ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；8-11 % PEG8000, 2.5 % MPD, 0.05 M MgAcetate, 0.05 M PCTP pH 8	Resolution 2.20 Å R-free 0.260
8QTJ Crystal structure of Cbl-b in complex with an allosteric inhibitor (compound 30) Deposited 2023-10-12	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–427（392 aa）	Not recorded	ZN ZINC ION × 2 NA SODIUM ION × 1 WUI 3-[3-[3-methyl-1-(4-methyl-1,2,4-triazol-3-yl)cyclobutyl]phenyl]-1-[(1~{R})-1-(1-methylpyrazol-4-yl)ethyl]-5-(trifluoromethyl)pyridin-2-one × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；8-11 % PEG8000, 2.5 % MPD, 0.05 M MgAcetate, 0.05 M PCTP pH 8	Resolution 1.52 Å R-free 0.232
8QTK Crystal structure of CBL-b in complex with an allosteric inhibitor (compound 31) Deposited 2023-10-12	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–427（392 aa）	Not recorded	ZN ZINC ION × 2 NA SODIUM ION × 1 WX9 3-[3-[3-methyl-1-(4-methyl-1,2,4-triazol-3-yl)cyclobutyl]phenyl]-1-[(1S)-1-(1-methylpyrazol-4-yl)ethyl]-5-(trifluoromethyl)pyridin-2-one × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；8-11 % PEG8000, 2.5 % MPD, 0.05 M MgAcetate, 0.05 M PCTP pH 8	Resolution 1.87 Å R-free 0.268
8VW4 Crystal structure of Cbl-b TKB bound to compound 26 Deposited 2024-01-31	Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–343（308 aa） Fragment：Cbl-PTB domain, residues 36-343	Not recorded	MG MAGNESIUM ION × 1 A1AEG (7-methoxy-2-{2-[(1S,3S,4S)-3-(3-methoxy-2-methyl-5-nitrophenyl)-1-methyl-5-oxo-1,5-dihydroimidazo[1,5-a]pyridin-2(3H)-yl]-2-oxoethoxy}quinolin-8-yl)acetic acid × 1 GOL GLYCEROL × 3	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；293 K；0.2 M NaCitrate, 20% PEG3350	Resolution 2.40 Å R-free 0.253
8VW4 Crystal structure of Cbl-b TKB bound to compound 26 Deposited 2024-01-31	Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain B 36–343（308 aa） Fragment：Cbl-PTB domain, residues 36-343	Not recorded	MG MAGNESIUM ION × 1 A1AEG (7-methoxy-2-{2-[(1S,3S,4S)-3-(3-methoxy-2-methyl-5-nitrophenyl)-1-methyl-5-oxo-1,5-dihydroimidazo[1,5-a]pyridin-2(3H)-yl]-2-oxoethoxy}quinolin-8-yl)acetic acid × 1 PEG DI(HYDROXYETHYL)ETHER × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；293 K；0.2 M NaCitrate, 20% PEG3350	Resolution 2.40 Å R-free 0.253
8VW5 Crystal structure of Cbl-b TKB bound to compound 2 Deposited 2024-01-31	Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–343（308 aa） Fragment：Cbl-PTB domain, residues 36-343	Not recorded	MG MAGNESIUM ION × 1 CA CALCIUM ION × 1 A1AD4 [5-(2-{(2R,5S)-2-[2-(carboxymethoxy)-3-methoxy-5-nitrophenyl]-3,5-dimethyl-4-oxoimidazolidin-1-yl}-2-oxoethyl)-3,6-dimethoxy-9,9-dimethyl-9H-xanthen-4-yl]acetic acid × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；293 K；0.2 M Ca(OAc)2, 0.1 M NaCacodylate pH 6.5, 18% PEG8000	Resolution 1.76 Å R-free 0.204
8VW5 Crystal structure of Cbl-b TKB bound to compound 2 Deposited 2024-01-31	Different construct Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain B 36–343（308 aa） Fragment：Cbl-PTB domain, residues 36-343	Not recorded	CA CALCIUM ION × 1 A1AD4 [5-(2-{(2R,5S)-2-[2-(carboxymethoxy)-3-methoxy-5-nitrophenyl]-3,5-dimethyl-4-oxoimidazolidin-1-yl}-2-oxoethyl)-3,6-dimethoxy-9,9-dimethyl-9H-xanthen-4-yl]acetic acid × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, HANGING DROP；293 K；0.2 M Ca(OAc)2, 0.1 M NaCacodylate pH 6.5, 18% PEG8000	Resolution 1.76 Å R-free 0.204
9FQH E3 ligase Cbl-b in complex with a triazolone core inhibitor (compound 1) Deposited 2024-06-17	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–427（392 aa）	Not recorded	A1IEW 8-[3-[3-methyl-1-(4-methyl-1,2,4-triazol-3-yl)cyclobutyl]phenyl]-3-[[(3~{S})-3-methylpiperidin-1-yl]methyl]-5-(trifluoromethyl)-1$l^{4},7,8-triazabicyclo[4.3.0]nona-1(6),2,4-trien-9-one × 1 ZN ZINC ION × 2 NA SODIUM ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；9 % PEG8000, 5 % MPD, 0.05 M MgAcetate, 0.05 M PCTP pH 8	Resolution 1.79 Å R-free 0.249
9FQI E3 ligase Cbl-b in complex with a lactam scaffold inhibitor (compound 7) Deposited 2024-06-17	Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–427（392 aa）	Not recorded	A1IEV 8-[3-[(4~{R})-4-methyl-2-oxidanylidene-piperidin-4-yl]phenyl]-3-[[(3~{S})-3-methylpiperidin-1-yl]methyl]-5-(trifluoromethyl)-1$l^{4},7,8-triazabicyclo[4.3.0]nona-1(6),2,4-trien-9-one × 1 ZN ZINC ION × 2 NA SODIUM ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；11 % PEG8000, 0.05 M Mg Acetate, 5 % MPD, 0.05 M PCPT pH 8.0	Resolution 1.95 Å R-free 0.291
9FQJ E3 ligase Cbl-b in complex with a carbamate scaffold inhibitor (compound 12) Deposited 2024-06-17	Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 1 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain A 36–427（392 aa）	Mutation：EC:2.3.2.27	A1IE5 2-cyclopropyl-6-methyl-~{N}-[3-[(6~{S})-6-methyl-2-oxidanylidene-1,3-oxazinan-6-yl]phenyl]pyrimidine-4-carboxamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；11 % PEG8000, 0.05 M Mg Acetate, 5 % MPD, 0.05 M PCPT pH 8.0	Resolution 1.56 Å R-free 0.222
9FQJ E3 ligase Cbl-b in complex with a carbamate scaffold inhibitor (compound 12) Deposited 2024-06-17	Different mutation/modification Different ligand/ion Different experimental conditions Different structure-quality metrics	Assembly 2 Protein monomer Monomer；Protein × 1 PDB declaration: monomeric	Chain B 36–427（392 aa）	Mutation：EC:2.3.2.27	A1IE5 2-cyclopropyl-6-methyl-~{N}-[3-[(6~{S})-6-methyl-2-oxidanylidene-1,3-oxazinan-6-yl]phenyl]pyrimidine-4-carboxamide × 1 ZN ZINC ION × 2 NA SODIUM ION × 1	X-RAY DIFFRACTION X-ray crystallization conditions VAPOR DIFFUSION, SITTING DROP；pH 8；293 K；11 % PEG8000, 0.05 M Mg Acetate, 5 % MPD, 0.05 M PCPT pH 8.0	Resolution 1.56 Å R-free 0.222

23 other PDB entries and 33 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence

UniProt name	CBLB_HUMAN
Isoform	—
PDB entities	1
Chains and sequence ranges	Author chain A； PDBConstruct 3–394； UniProt 36–427

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

SAXS scattering curve SAXS Profile

P(r) Distance Distribution P(r) Distribution

Download Download SAXS (.dat) P(r) (.pr.out) CIF

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2. Structure Basics 2. Structure Basics

Entry ID entry_id	8qng
Deposition date deposition_date	2023-09-26
Structure title title	Crystal structure of the E3 ubiquitin ligase Cbl-b with an allosteric inhibitor (benzodiazepine HTS hit compound 1)
Keywords keywords	E3 Ubiquitin ligase, allosteric inhibition, structure based drug design, LIGASE; LIGASE
Experimental Method method	X-RAY DIFFRACTION

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3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier	23.19 Å
Radius of gyration Rg (electron density) rg_electron	21.81 Å
Forward intensity I(0) i0	32380500.00
Molecular weight molecular_weight	44485.0 kDa
Excluded volume excluded_volume	55931 Å³
Envelope volume envelope_volume	65605 Å³
Hydration-shell volume shell_volume	25020 Å³
Envelope diameter envelope_diameter	72.8 Å
Shell Rg shell_rg	28.90 Å
Envelope Rg envelope_rg	22.08 Å
Shape Rg shape_rg	21.78 Å
Total Rg total_rg	22.79 Å
Total atoms total_atoms	3124
Residues n_residues	384
Spherical-harmonic order n_harmonics	20
q range q_range	— – 0.5000 Å⁻¹
Data points n_points	101
Shell type shell_type	directional
Solvent electron density solvent_density	0.3340 e/Å³
Shell contrast contrast_shell	0.0300 e/Å³
CRYSOL version crysol_version	4.1.3

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4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

Maximum dimension Dmax dmax	70.8 Å
Rg (real space) rg_real	23.06 Å
Rg uncertainty (real space) rg_real_error	0.38 Å
I(0) (real space) i0_real	3.2380e+07
I(0) uncertainty (real space) i0_real_error	3.9620e+05
Rg (reciprocal space) rg_reciprocal	23.09 Å
I(0) (reciprocal space) i0_reciprocal	32380000.0000
Solution quality estimate total_estimate	0.9111
Solution quality rating solution_quality	EXCELLENT a EXCELLENT solution
P(r) peaks n_peaks	2
Primary peak position r_peak_primary	29.4 Å
Skewness Skewness skewness	0.120
Kurtosis Kurtosis kurtosis	-0.537
Angular range angular_range	— – 0.3400 Å⁻¹
Current regularization parameter α current_alpha	0.0000
Highest regularization parameter α highest_alpha	7940000.0000
Real-space data points n_real_points	66
GNOM version gnom_version	4.1.3
Quality Criteria quality_criteria	AN1: 0.000; Oscil: 0.950; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.993; Smooth: 0.998

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5. Crystallography and Experiment 5. Crystallography & Experiment

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6. Entities and Polymers Entities & Polymers (5)

Entity 1 Entity 1 polymer

Description description	E3 ubiquitin-protein ligase CBL-B
Molecular weight formula_weight	45809.5 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A
Atom count atom_count	3144

HMPKQAAADRRTVEKTWKLMDKVVRLCQNPKLQLKNSPPYILDILPDTYQHLRLILSKYDDNQKLAQLSENEYFKIYIDSLMKKSKRAIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHMLAEIKAIFPNGQFQGDNFRITKADAAEFWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWGSILRNWNFLAVTHPGYMAFLTYDEVKARLQKYSTKPGSYIFRLSCTRLGQWAIGYVTGDGNILQTIPHNKPLFQALIDGSREGFYLYPDGRSYNPDLTGLCEPTPHDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTAWQESDGQGCPFCRCEIKGTEPIIVDPFD

来源 Source

来源生物 organism	Homo sapiens
通用名 common_name	human
NCBI Class编号 ncbi_taxonomy_id	9606
宿主生物 host_organism	Escherichia coli

Entity 2 Entity 2 non-polymer

Description description	2-(morpholin-4-ylmethyl)-~{N}-[(3~{S})-2-oxidanylidene-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]benzamide
Molecular weight formula_weight	454.5 kDa
Source method src_method	syn
Copy count entity_count	1

Entity 3 Entity 3 non-polymer

Description description	ZINC ION
Molecular weight formula_weight	65.4 kDa
Source method src_method	syn
Copy count entity_count	2

Entity 4 Entity 4 non-polymer

Description description	SODIUM ION
Molecular weight formula_weight	23.0 kDa
Source method src_method	syn
Copy count entity_count	1

Entity 5 Entity 5 water

Description description	water
Molecular weight formula_weight	18.0 kDa
Source method src_method	nat
Copy count entity_count	20

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8. Citations (1)

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Unit-cell length a length_a	55.578 Å
Unit-cell length b length_b	72.045 Å
Unit-cell length c length_c	94.786 Å
Unit-cell angle α angle_alpha	90.00 °
Unit-cell angle β angle_beta	90.00 °
Unit-cell angle γ angle_gamma	90.00 °
Molecules per unit cell Z z_pdb	4

Space group space_group	P 21 21 21
Space-group number int_tables_number	19
Crystal system crystal_system	—

Resolution resolution	2.197 Å
Low-resolution limit resolution_low	47.940 Å
R factor r_factor	0.2224
R_work r_work	0.2187
R_free r_free	0.2949

fit	/app/data/saxs_computation/qn/8qng/8qng.fit
pddf	/app/data/pr_computation/qn/8qng/8qng.pr.out
profile	/app/data/saxs_computation/qn/8qng/8qng.dat