PDBsum entry 5jlb

Transferase

PDB id: 5jlb

Contents

Protein chains

248 a.a.

14 a.a.

Ligands

SAH

SCN ×3

GOL ×2

Metals

_ZN ×3

Waters ×330

PDB id:

5jlb

Name:

Transferase

Title:

Crystal structure of setd2 bound to histone h3.3 k36i peptide

Structure:

Histone-lysine n-methyltransferase setd2. Chain: a. Fragment: catalytic domain, unp residues 1434-1711. Synonym: hif-1,huntingtin yeast partner b,huntingtin-interacting protein 1,hip-1,huntingtin-interacting protein b,lysine n- methyltransferase 3a,set domain-containing protein 2,hset2,p231hbp. Engineered: yes. Histone h3.3. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: setd2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: chemically synthesized

Resolution:

1.50Å R-factor: 0.166 R-free: 0.190

Authors:

H.Li,S.Yang

Key ref:

S.Yang et al. (2016). Molecular basis for oncohistone H3 recognition by SETD2 methyltransferase. Genes Dev, 30, 1611-1616. PubMed id: 27474439 DOI: 10.1101/gad.284323.116

Date:

26-Apr-16 Release date: 02-Nov-16

Protein chain

Q9BYW2  (SETD2_HUMAN) -  Histone-lysine N-methyltransferase SETD2 from Homo sapiens

Seq: 2564 a.a.

Struc: 248 a.a.

Protein chain

P84243  (H33_HUMAN) -  Histone H3.3 from Homo sapiens

Seq: 136 a.a.

Struc: 14 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chain A: E.C.2.1.1.359 - [histone H3]-lysine(36) N-trimethyltransferase.
• Reaction: L-lysyl₃₆-[histone H3] + 3 S-adenosyl-L-methionine = N₆,N₆,N₆- trimethyl-L-lysyl₃₆-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H⁺

L-lysyl(36)-[histone H3] + 3 × S-adenosyl-L-methionine = N(6),N(6),N(6)- trimethyl-L-lysyl(36)-[histone H3] + 3 × S-adenosyl-L-homocysteine + 3 × H(+) (Bound ligand (Het Group name = SAH) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1101/gad.284323.116

Genes Dev 30:1611-1616 (2016)

PubMed id: 27474439

Molecular basis for oncohistone H3 recognition by SETD2 methyltransferase.

S.Yang, X.Zheng, C.Lu, G.M.Li, C.D.Allis, H.Li.

ABSTRACT

High-frequency point mutations of genes encoding histones have been identified recently as novel drivers in a number of tumors. Specifically, the H3K36M/I mutations were shown to be oncogenic in chondroblastomas and undifferentiated sarcomas by inhibiting H3K36 methyltransferases, including SETD2. Here we report the crystal structures of the SETD2 catalytic domain bound to H3K36M or H3K36I peptides with SAH (S-adenosylhomocysteine). In the complex structure, the catalytic domain adopts an open conformation, with the K36M/I peptide snuggly positioned in a newly formed substrate channel. Our structural and biochemical data reveal the molecular basis underying oncohistone recognition by and inhibition of SETD2.