8QNI: E3 ubiquitin-protein ligase CBL-B

Name: PDB 8QNI: Crystal structure of the E3 ubiquitin ligase Cbl-b with an allosteric inhibitor (benzodiazepine compound 25)
Published: 2023-11-22
License: https://creativecommons.org/publicdomain/zero/1.0/
Keywords: ligase

Crystal structure of the E3 ubiquitin ligase Cbl-b with an allosteric inhibitor (benzodiazepine compound 25). Determined by X-ray diffraction at 2.48 Å resolution. Released 22 Nov 2023.

Method: X-ray diffraction
Resolution: 2.48 Å
Organism: Homo sapiens
Chains: 1
Atoms: 3,094
Mol. weight: 46.43 kDa
Ligands: ZN, W7R
Released: 22 Nov 2023

Explore 8QNI in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8QNI contains 22 α-helices and 13 β-strands across 1 chain. 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: 22 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	43-60	18
α-helix	63-65	3
α-helix	74-91	18
α-helix	95-103	9
α-helix	105-128	24
α-helix	131-133	3
α-helix	138-160	23
α-helix	162-164	3
α-helix	168-170	3
α-helix	171-173	3
α-helix	176-186	11
β-strand	191-193	3	1
α-helix	194-204	11
α-helix	210-220	11
β-strand	227-229	3	1
α-helix	230-239	10
α-helix	243-245	3
α-helix	246-250	5
α-helix	251-255	5
β-strand	260-263	4	2
α-helix	266-274	9
β-strand	282-288	7	2
β-strand	291-300	10	2
β-strand	306-309	4	2
α-helix	316-325	10
β-strand	331-332	2	2
α-helix	342-344	3
α-helix	357-367	11
β-strand	372	1	3
β-strand	380	1	3
β-strand	383-384	2	4
β-strand	385-386	2	5
β-strand	391-392	2	4
α-helix	394-401	8
β-strand	417-418	2	5

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
E3 ubiquitin-protein ligase CBL-B	A	protein	394	Homo sapiens	Q13191 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8QNI_1 E3 ubiquitin-protein ligase CBL-B (chains A)
HMPKQAAADRRTVEKTWKLMDKVVRLCQNPKLQLKNSPPYILDILPDTYQHLRLILSKYD
DNQKLAQLSENEYFKIYIDSLMKKSKRAIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHM
LAEIKAIFPNGQFQGDNFRITKADAAEFWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEA
MALKSTIDLTCNDYISVFEFDIFTRLFQPWGSILRNWNFLAVTHPGYMAFLTYDEVKARL
QKYSTKPGSYIFRLSCTRLGQWAIGYVTGDGNILQTIPHNKPLFQALIDGSREGFYLYPD
GRSYNPDLTGLCEPTPHDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMC
TSCLTAWQESDGQGCPFCRCEIKGTEPIIVDPFD

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	2
W7R	2-[[(2~{S})-2-methylmorpholin-4-yl]methyl]-~{N}-[(3~{S})-2-oxidanylidene-5-phen…	C27 H27 N5 O3	1

Water and common crystallization additives (NA) are not listed.

Primary citation

Discovery of a Novel Benzodiazepine Series of Cbl-b Inhibitors for the Enhancement of Antitumor Immunity. Boerth, J.A., Chinn, A.J., Schimpl, M. et al. ACS Med Chem Lett (2023) 14:1848-1856. DOI 10.1021/acsmedchemlett.3c00439 · PubMed

Other PDB entries of the same protein (UniProt Q13191 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8QTG 1.42 Å, Crystal structure of CBL-b in complex with an allosteric inhibitor (compound 9)
8QTJ 1.52 Å, Crystal structure of Cbl-b in complex with an allosteric inhibitor (compound 30)
2OOA 1.56 Å, crystal structure of the UBA domain from Cbl-b ubiquitin ligase
9FQJ 1.56 Å, E3 ligase Cbl-b in complex with a carbamate scaffold inhibitor (compound 12)
9XZD 1.65 Å, E3 ubiquitin-protein ligase CBL-B in complex with compound 8
9I0B 1.66 Å, E3 ubiquitin ligase CBL-B in complex with inhibitor
2J6F 1.7 Å, N-terminal SH3 domain of cms (CD2AP human homolog) bound to cbl-B peptide
9XZB 1.75 Å, E3 ubiquitin-protein ligase CBL-B in complex with compound 2
8VW5 1.76 Å, Crystal structure of Cbl-b TKB bound to compound 2
10ZJ 1.77 Å, Structure of Cbl-B bound to compound 8
9FQH 1.79 Å, E3 ligase Cbl-b in complex with a triazolone core inhibitor (compound 1)
9XZC 1.8 Å, E3 ubiquitin-protein ligase CBL-B in complex with compound 6

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