9KN9: NSD2-PWWP1 domain

NSD2-PWWP1 domain bound with compound 1. Determined by X-ray diffraction at 2.0 Å resolution. Released 26 Nov 2025.

Method: X-ray diffraction
Resolution: 2.0 Å
Organism: Homo sapiens
Chains: 2
Atoms: 2,135
Mol. weight: 31.24 kDa
Ligands: A1EF6
Released: 26 Nov 2025

Explore 9KN9 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9KN9 contains 14 α-helices and 12 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: 7 helices, 6 β-strands

Element	Residues	Length	Sheet
β-strand	225-228	4	2
β-strand	236-240	5	2
β-strand	250-252	3	2
β-strand	260-266	7	2
β-strand	272-277	6	2
α-helix	278-280	3
β-strand	281-283	3	2
α-helix	287-289	3
α-helix	290-300	11
α-helix	304-310	7
α-helix	313-314	2
α-helix	316-333	18
α-helix	337-344	8

Chain B: 7 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	218-220	3
β-strand	225-228	4	1
β-strand	236-240	5	1
β-strand	250-252	3	1
β-strand	260-266	7	1
β-strand	272-277	6	1
α-helix	278-280	3
β-strand	281-283	3	1
α-helix	289-298	10
α-helix	304-311	8
α-helix	313-314	2
α-helix	316-333	18
α-helix	337-344	8

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histone-lysine N-methyltransferase NSD2	A, B	protein	133	Homo sapiens	O96028 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>9KN9_1 Histone-lysine N-methyltransferase NSD2 (chains A, B)
LLKYNVGDLVWSKVSGYPWWPCMVSADPLLHSYTKLKGQKKSARQYHVQFFGDAPERAWI
FEKSLVAFEGEGQFEKLCQESAKQAPTKAEKIKLLKPISGKLRAQWEMGIVQAEEAASMS
VEERKAKFTFLYV

Ligands and cofactors

ID	Name	Formula	Copies
A1EF6	(Z)-N-methyl-3-sulfanyl-prop-2-enamide	C4 H7 N O S	2

Water and common crystallization additives (SO4, EPE) are not listed.

Primary citation

Fragment-Based Screening of NSD2-PWWP1 Identifies Novel Covalent Allosteric Ligands That Diminish Methyllysine and DNA Binding Abilities of NSD2. Huang, Y., Li, Y., Chen, X. et al. J Med Chem (2025) 68:24953-24967. DOI 10.1021/acs.jmedchem.5c01902 · PubMed

Other PDB entries of the same protein (UniProt O96028 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9FOC 1.62 Å, Crystal structure of the PWWP1 domain of NSD2 bound by compound 11.
6XCG 1.64 Å, Histone-lysine N-methyltransferase NSD2-PWWP1 with compound UNC6934
9EXY 1.7 Å, Crystal structure of the PWWP1 domain of NSD2 bound by compound 34.
9GBF 1.76 Å, X-RAY structure of PHDvC5HCH tandem domain of NSD2
5VC8 1.8 Å, Crystal structure of the WHSC1 PWWP1 domain
9KNB 1.84 Å, NSD2-PWWP1 domain bound with compound 9
9EXX 1.94 Å, Crystal structure of the PWWP1 domain of NSD2 bound by compound 18.
9FOE 1.96 Å, Crystal structure of the PWWP1 domain of NSD2 bound by compound 7.
9Y60 2.02 Å, Crystal structure of NSD2 PWWP1 domain in complex with (6R)-6-(3,5-dichlorophenyl)morphol…
5LSU 2.14 Å, Structure of the Epigenetic Oncogene MMSET and inhibition by N-Alkyl Sinefungin…
7LMT 2.27 Å, Histone-lysine N-methyltransferase NSD2-PWWP1 with compound MRT10241866a
6UE6 2.4 Å, PWWP1 domain of NSD2 in complex with MR837

Browse structure collections

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