8QTH: CBL-b

Crystal structure of CBL-b in complex with an allosteric inhibitor (compound 8). Determined by X-ray diffraction at 2.2 Å resolution. Released 10 Jan 2024.

Method: X-ray diffraction
Resolution: 2.2 Å
Organism: Homo sapiens
Chains: 1
Atoms: 3,170
Mol. weight: 46.4 kDa
Ligands: WX0, ZN
Released: 10 Jan 2024

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

Secondary structure: helices and β-sheets

8QTH contains 23 α-helices and 12 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: 23 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	38-40	3
α-helix	43-60	18
α-helix	63-65	3
α-helix	74-91	18
α-helix	95-102	8
α-helix	105-128	24
α-helix	129-133	5
α-helix	138-160	23
α-helix	162-164	3
α-helix	168-170	3
α-helix	176-186	11
β-strand	191-193	3	1
α-helix	194-202	9
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	266-273	8
α-helix	274-276	3
β-strand	282-287	6	2
β-strand	295-300	6	2
β-strand	306-309	4	2
α-helix	316-326	11
β-strand	331-332	2	2
α-helix	342-344	3
α-helix	357-364	8
β-strand	372	1	3
β-strand	380	1	3
β-strand	383-386	4	4
β-strand	391-392	2	4
α-helix	394-402	9
β-strand	417-420	4	4

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

>8QTH_1 E3 ubiquitin-protein ligase CBL-B (chains A)
HMPKQAAADRRTVEKTWKLMDKVVRLCQNPKLQLKNSPPYILDILPDTYQHLRLILSKYD
DNQKLAQLSENEYFKIYIDSLMKKSKRAIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHM
LAEIKAIFPNGQFQGDNFRITKADAAEFWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEA
MALKSTIDLTCNDYISVFEFDIFTRLFQPWGSILRNWNFLAVTHPGYMAFLTYDEVKARL
QKYSTKPGSYIFRLSCTRLGQWAIGYVTGDGNILQTIPHNKPLFQALIDGSREGFYLYPD
GRSYNPDLTGLCEPTPHDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMC
TSCLTAWQESDGQGCPFCRCEIKGTEPIIVDPFD

Ligands and cofactors

ID	Name	Formula	Copies
WX0	1-methyl-5-[3-[3-methyl-1-(4-methyl-1,2,4-triazol-3-yl)cyclobutyl]phenyl]-3-(tr…	C23 H22 F3 N5 O	1
ZN	Zinc ion	Zn	2

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

Primary citation

Discovery, Optimization, and Biological Evaluation of Arylpyridones as Cbl-b Inhibitors. Mfuh, A.M., Boerth, J.A., Bommakanti, G. et al. J Med Chem (2024) 67:1500-1512. DOI 10.1021/acs.jmedchem.3c02083 · 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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