PDBsum entry 4l58

Transferase

PDB id: 4l58

Contents

Protein chain

65 a.a.

Ligands

ALA-ARG-THR-M3L-GLN-THR-ALA

Metals

_ZN ×2

Waters ×125

PDB id:

4l58

Name:

Transferase

Title:

Crystal structure of the mll5 phd finger in complex with h3k4me3

Structure:

Histone-lysine n-methyltransferase mll5. Chain: a. Fragment: phd-type zinc finger domain residues 117-181. Synonym: lysine n-methyltransferase 2e, kmt2e, myeloid/lymphoid or mixed-lineage leukemia protein 5. Engineered: yes. Histone h3 peptide. Chain: b. Synonym: h3k4me3 peptide.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mll5, kmt2e. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the modified peptide was synthesized.

Resolution:

1.48Å R-factor: 0.126 R-free: 0.140

Authors:

Q.Tong,M.Ali,T.G.Kutateladze

Key ref:

M.Ali et al. (2013). Molecular basis for chromatin binding and regulation of MLL5. Proc Natl Acad Sci U S A, 110, 11296-11301. PubMed id: 23798402 DOI: 10.1073/pnas.1310156110

Date:

10-Jun-13 Release date: 26-Jun-13

Protein chain

Q8IZD2  (KMT2E_HUMAN) -  Inactive histone-lysine N-methyltransferase 2E from Homo sapiens

Seq: 1858 a.a.

Struc: 65 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.1.43 - Transferred entry: 2.1.1.354.
• Reaction: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N₆-methyl-L-lysine-[histone]

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

Added reference

DOI no: 10.1073/pnas.1310156110

Proc Natl Acad Sci U S A 110:11296-11301 (2013)

PubMed id: 23798402

Molecular basis for chromatin binding and regulation of MLL5.

M.Ali, H.Rincón-Arano, W.Zhao, S.B.Rothbart, Q.Tong, S.M.Parkhurst, B.D.Strahl, L.W.Deng, M.Groudine, T.G.Kutateladze.

ABSTRACT

The human mixed-lineage leukemia 5 (MLL5) protein mediates hematopoietic cell homeostasis, cell cycle, and survival; however, the molecular basis underlying MLL5 activities remains unknown. Here, we show that MLL5 is recruited to gene-rich euchromatic regions via the interaction of its plant homeodomain finger with the histone mark H3K4me3. The 1.48-Å resolution crystal structure of MLL5 plant homeodomain in complex with the H3K4me3 peptide reveals a noncanonical binding mechanism, whereby K4me3 is recognized through a single aromatic residue and an aspartate. The binding induces a unique His-Asp swapping rearrangement mediated by a C-terminal α-helix. Phosphorylation of H3T3 and H3T6 abrogates the association with H3K4me3 in vitro and in vivo, releasing MLL5 from chromatin in mitosis. This regulatory switch is conserved in the Drosophila ortholog of MLL5, UpSET, and suggests the developmental control for targeting of H3K4me3. Together, our findings provide first insights into the molecular basis for the recruitment, exclusion, and regulation of MLL5 at chromatin.