8VW4: Cbl-b TKB

Crystal structure of Cbl-b TKB bound to compound 26. Determined by X-ray diffraction at 2.4 Å resolution. Released 3 Jul 2024.

Method: X-ray diffraction
Resolution: 2.4 Å
Organism: Homo sapiens
Chains: 2
Atoms: 5,301
Mol. weight: 73.99 kDa
Ligands: A1AEG, MG
Released: 3 Jul 2024

Explore 8VW4 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8VW4 contains 38 α-helices and 14 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: 19 helices, 7 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	129-132	4
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	194-204	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	282-287	6	2
β-strand	295-300	6	2
β-strand	306-309	4	2
α-helix	316-325	10
β-strand	331-332	2	2
α-helix	338-340	3

Chain B: 19 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	43-60	18
α-helix	63-65	3
α-helix	74-94	21
α-helix	98-103	6
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	3
α-helix	194-204	11
α-helix	210-220	11
β-strand	227-229	3	3
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	4
α-helix	266-273	8
α-helix	274-276	3
β-strand	282-287	6	4
β-strand	296-300	5	4
β-strand	306-309	4	4
α-helix	316-325	10
β-strand	331-332	2	4

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
E3 ubiquitin-protein ligase CBL-B	A, B	protein	310	Homo sapiens	Q13191 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8VW4_1 E3 ubiquitin-protein ligase CBL-B (chains A, B)
GSPKQAAADRRTVEKTWKLMDKVVRLCQNPKLQLKNSPPYILDILPDTYQHLRLILSKYD
DNQKLAQLSENEYFKIYIDSLMKKSKRAIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHM
LAEIKAIFPNGQFQGDNFRITKADAAEFWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEA
MALKSTIDLTCNDYISVFEFDIFTRLFQPWGSILRNWNFLAVTHPGYMAFLTYDEVKARL
QKYSTKPGSYIFRLSCTRLGQWAIGYVTGDGNILQTIPHNKPLFQALIDGSREGFYLYPD
GRSYNPDLTG

Ligands and cofactors

ID	Name	Formula	Copies
A1AEG	(7-methoxy-2-{2-[(1S,3S,4S)-3-(3-methoxy-2-methyl-5-nitrophenyl)-1-methyl-5-oxo…	C30 H28 N4 O9	2
MG	Magnesium ion	Mg	2

Water and common crystallization additives (PEG, GOL) are not listed.

Primary citation

Optimization of a Novel DEL Hit That Binds in the Cbl-b SH2 Domain and Blocks Substrate Binding. Liang, J., Lambrecht, M.J., Arenzana, T.L. et al. ACS Med Chem Lett (2024) 15:864-872. DOI 10.1021/acsmedchemlett.4c00068 · 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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