8RZU: Human SETD2 L1609P mutant

Name: PDB 8RZU: Structure of human SETD2 L1609P mutant in complex with SAM and H3K36M peptide
Published: 2025-03-05
License: https://creativecommons.org/publicdomain/zero/1.0/
Keywords: transferase

Structure of human SETD2 L1609P mutant in complex with SAM and H3K36M peptide. Determined by X-ray diffraction at 2.19 Å resolution. Released 5 Mar 2025.

Method: X-ray diffraction
Resolution: 2.19 Å
Organism: Homo sapiens
Chains: 2
Atoms: 2,151
Mol. weight: 36.24 kDa
Ligands: SAM, ZN
Released: 5 Mar 2025

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

Secondary structure: helices and β-sheets

8RZU contains 14 α-helices and 25 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: 14 helices, 23 β-strands

Element	Residues	Length	Sheet
β-strand	1448-1450	3	1
α-helix	1451-1455	5
α-helix	1457-1465	9
α-helix	1470-1472	3
β-strand	1474-1475	2	2
β-strand	1480-1481	2	3
α-helix	1501-1505	5
α-helix	1506-1511	6
β-strand	1515	1	4
α-helix	1521-1524	4
β-strand	1527	1	5
α-helix	1536-1538	3
β-strand	1539	1	4
α-helix	1543-1546	4
β-strand	1552-1556	5	1
β-strand	1562-1566	5	1
β-strand	1570	1	6
β-strand	1575-1578	4	5
β-strand	1582-1584	3	3
α-helix	1586-1599	14
β-strand	1606-1607	2	3
β-strand	1614-1616	3	3
β-strand	1620-1621	2	2
α-helix	1623-1626	4
α-helix	1627	1
β-strand	1628-1629	2	7
β-strand	1635-1642	8	5
β-strand	1645-1652	8	5
β-strand	1656	1	6
α-helix	1657	1
α-helix	1660	1
β-strand	1661-1662	2	1
β-strand	1663-1664	2	7
β-strand	1669-1670	2	8
β-strand	1677	1	9
β-strand	1688	1	9
α-helix	1697-1700	4

Chain B: 0 helices, 2 β-strands

Element	Residues	Length	Sheet
β-strand	34-35	2	8
β-strand	36	1	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histone-lysine N-methyltransferase SETD2	A	protein	295	Homo sapiens	Q9BYW2 (AlphaFold model)
Histone H3	B	protein	14	Homo sapiens	P84243 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8RZU_1 Histone-lysine N-methyltransferase SETD2 (chains A)
MHHHHHHSSGRENLYFQGETSVPPGSALVGPSCVMDDFRDPQRWKECAKQGKMPCYFDLI
EENVYLTERKKNKSHRDIKRMQCECTPLSKDERAQGEIACGEDCLNRLLMIECSSRCPNG
DYCSNRRFQRKQHADVEVILTEKKGWGLRAAKDLPSNTFVLEYCGEVLDHKEFKARVKEY
ARNKNIHYYFMAPKNDEIIDATQKGNCSRFMNHSCEPNCETQKWTVNGQLRVGFFTTKLV
PSGSELTFDYQFQRYGKEAQKCFCGSANCRGYLGGENRVSIRAAGGKMKKERSRK

Sequence of entity 2 (B), FASTA

>8RZU_2 Histone H3 (chains B)
APSTGGVMKPHRYR

Ligands and cofactors

ID	Name	Formula	Copies
SAM	S-adenosylmethionine	C15 H22 N6 O5 S	1
ZN	Zinc ion	Zn	3

Primary citation

The SETD2 L1609P mutation found in leukemia disrupts methyltransferase activity and reduces histone H3K36 trimethylation. Michail, C., Berthelet, J., Mechaly, A.E. et al. J Biol Chem (2026) 302:111259-111259. DOI 10.1016/j.jbc.2026.111259 · PubMed

Other PDB entries of the same protein (UniProt Q9BYW2 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5JLB 1.5 Å, Crystal structure of SETD2 bound to histone H3.3 K36I peptide
5LT7 1.51 Å, Structure of the Epigenetic Oncogene MMSET and inhibition by N-Alkyl Sinefungin…
5LT8 1.57 Å, Structure of the Epigenetic Oncogene MMSET and inhibition by N-Alkyl Sinefungin…
7EVS 1.6 Å, Crystal structure of hnRNP LL RRM2 in complex with SETD2
5LSY 1.62 Å, Structure of the Epigenetic Oncogene MMSET and inhibition by N-Alkyl Sinefungin…
5LSZ 1.62 Å, Structure of the Epigenetic Oncogene MMSET and inhibition by N-Alkyl Sinefungin…
9G4A 1.65 Å, Structure of human SETD2 T1663M mutant in complex with SAM and H3K36M peptide
6J9J 1.78 Å, crystal structure of SESTD2 in complex with H3.3S31phK36M peptide
5LSS 1.79 Å, Structure of the Epigenetic Oncogene MMSET and inhibition by N-Alkyl Sinefungin…
7EVR 1.8 Å, Crystal structure of hnRNP L RRM2 in complex with SETD2
7LZD 1.8 Å, Crystal Structure of SETD2 bound to Compound 35
8Q5P 1.81 Å, Structure of the lysine methyltransferase SETD2 in complex with a peptide derived from…

Browse structure collections

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