9FQJ: E3 ligase Cbl-b

Name: PDB 9FQJ: E3 ligase Cbl-b in complex with a carbamate scaffold inhibitor (compound 12)
Published: 2024-07-31
License: https://creativecommons.org/publicdomain/zero/1.0/
Keywords: ligase

E3 ligase Cbl-b in complex with a carbamate scaffold inhibitor (compound 12). Determined by X-ray diffraction at 1.56 Å resolution. Released 31 Jul 2024.

Method: X-ray diffraction
Resolution: 1.56 Å
Organism: Homo sapiens
Chains: 2
Atoms: 6,747
Mol. weight: 92.66 kDa
Ligands: ZN, A1IE5
Released: 31 Jul 2024

Explore 9FQJ in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9FQJ contains 44 α-helices and 24 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: 22 helices, 12 β-strands

Element	Residues	Length	Sheet
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	251-256	6
β-strand	260-263	4	2
α-helix	266-273	8
α-helix	274-276	3
β-strand	282-287	6	2
β-strand	296-300	5	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	357-364	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

Chain B: 22 helices, 12 β-strands

Element	Residues	Length	Sheet
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	5
α-helix	194-202	9
α-helix	210-220	11
β-strand	227-229	3	5
α-helix	230-239	10
α-helix	243-245	3
α-helix	246-250	5
α-helix	251-256	6
β-strand	260-263	4	6
α-helix	266-273	8
α-helix	274-276	3
β-strand	282-287	6	6
β-strand	295-300	6	6
β-strand	306-309	4	6
α-helix	316-325	10
β-strand	331-332	2	6
α-helix	342-344	3
α-helix	357-364	8
β-strand	372	1	7
β-strand	380	1	7
β-strand	383-386	4	8
β-strand	391-392	2	8
α-helix	394-402	9
β-strand	417-420	4	8

Molecules and chains

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

Sequence of entity 1 (A, B), FASTA

>9FQJ_1 E3 ubiquitin-protein ligase CBL-B (chains A, B)
HMPKQAAADRRTVEKTWKLMDKVVRLCQNPKLQLKNSPPYILDILPDTYQHLRLILSKYD
DNQKLAQLSENEYFKIYIDSLMKKSKRAIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHM
LAEIKAIFPNGQFQGDNFRITKADAAEFWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEA
MALKSTIDLTCNDYISVFEFDIFTRLFQPWGSILRNWNFLAVTHPGYMAFLTYDEVKARL
QKYSTKPGSYIFRLSCTRLGQWAIGYVTGDGNILQTIPHNKPLFQALIDGSREGFYLYPD
GRSYNPDLTGLCEPTPHDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMC
TSCLTAWQESDGQGCPFCRCEIKGTEPIIVDPFD

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	4
A1IE5	2-cyclopropyl-6-methyl-~{N}-[3-[(6~{S})-6-methyl-2-oxidanylidene-1,3-oxazinan-6…	C20 H22 N4 O3	2

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

Primary citation

Accelerated Discovery of Carbamate Cbl-b Inhibitors Using Generative AI Models and Structure-Based Drug Design. Quinn, T.R., Giblin, K.A., Thomson, C. et al. J Med Chem (2024) 67:14210-14233. DOI 10.1021/acs.jmedchem.4c01034 · 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
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
8GCY 1.81 Å, Co-crystal structure of CBL-B in complex with N-Aryl isoindolin-1-one inhibitor

Browse structure collections

About this viewer

MolViewer shows 9FQJ directly in your browser with nothing to install. Switch between cartoon, ball-and-stick, spacefill and surface views, color by chain, secondary structure or B-factor, measure distances, angles and dihedrals, and share or embed the view.