9DOM: Protein cereblon

PVTX-405: A Potent, Highly Selective, and Orally Efficacious Molecular Glue Degrader of IKZF2 for Cancer Immunotherapy. Determined by X-ray diffraction at 1.69 Å resolution. Released 14 May 2025.

Method: X-ray diffraction
Resolution: 1.69 Å
Organism: Homo sapiens
Chains: 8
Atoms: 4,636
Mol. weight: 64.74 kDa
Ligands: ZN, A1A8N
Released: 14 May 2025

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

Secondary structure: helices and β-sheets

9DOM contains 12 α-helices and 48 β-strands across 8 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.

Chains A, C, E and G: 2 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	320-323	4	1
β-strand	330-333	4	1
α-helix	334-336	3
β-strand	337	1	2
β-strand	346-350	5	2
β-strand	356-362	7	2
β-strand	368-375	8	2
β-strand	384-391	8	2
β-strand	397-404	8	2
β-strand	413-418	6	2
α-helix	419-421	3
β-strand	422-423	2	1

Chains B, D and F: 1 helix, 2 β-strands

Element	Residues	Length	Sheet
β-strand	140-141	2	3
β-strand	148-149	2	3
α-helix	152-162	11

Chain H: 1 helix, 2 β-strands

Element	Residues	Length	Sheet
β-strand	140-141	2	12
β-strand	148-149	2	12
α-helix	152-161	10

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Protein cereblon	A, C, E, G	protein	111	Homo sapiens	Q96SW2 (AlphaFold model)
Zinc finger protein Helios	B, D, F, H	protein	30	Homo sapiens	Q9UKS7 (AlphaFold model)

Sequence of entity 1 (A, C, E, G), FASTA

>9DOM_1 Protein cereblon (chains A, C, E, G)
GPSTSLSCKQCQETEITTKNEIFSLSLSGPMAAYVNPHGYVHETLTVYKASNLNLIGRPS
TEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTI

Sequence of entity 2 (B, D, F, H), FASTA

>9DOM_2 Zinc finger protein Helios (chains B, D, F, H)
GGERPFHCNQCGASFTQKGNLLRHIKLHSG

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	8
A1A8N	(3S)-3-(1'-benzyl-6-oxo-6,8-dihydro-2H,7H-spiro[furo[2,3-e]isoindole-3,4'-piper…	C26 H27 N3 O4	4

Primary citation

Development of PVTX-405 as a potent and highly selective molecular glue degrader of IKZF2 for cancer immunotherapy. Chen, Z., Dhruv, H., Zhang, X. et al. Nat Commun (2025) 16:4095-4095. DOI 10.1038/s41467-025-58431-z · PubMed

Other PDB entries of the same protein (UniProt Q96SW2 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4M91 1.1 Å, crystal structure of hN33/Tusc3-peptide 1
9CUO 1.6 Å, Crystal structure of CRBN with compound 3
9OHQ 1.6 Å, Structure of CRBN:IKZF2:Compound 15
7BQV 1.8 Å, Cereblon in complex with SALL4 and (S)-5-hydroxythalidomide
9O91 1.86 Å, Structure of IKZF2:CRBN:Compound 5 ternary structure
7BQU 1.9 Å, Cereblon in complex with SALL4 and (S)-thalidomide
9GAO 1.95 Å, Crystal structure of CRBNmidi in complex with 2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)-N-me…
9FJX 2.0 Å, Crystal structure of human CRBN-DDB1 in complex with Lenalidomide
8RQC 2.15 Å, Crystal structure of CRBN-midi in complex with mezigdomide and IKZF1 ZF2
8RQ8 2.19 Å, Crystal structure of CRBN-midi in complex with mezigdomide
9OHR 2.34 Å, Structure of CRBN:IKZF2:Compound 35
9SFM 2.39 Å, Crystal structure of Cereblon-DDB1 in complex with SB-405483 and Lenalidomide

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