PDBsum entry 3lqi

Transferase

PDB id

3lqi

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Contents

			Protein chain

					176 a.a. *

			Ligands

					ALA-ARG-THR-MLY- GLN-THR


					ALA-ARG-THR-MLY- GLN-THR-ALA


					ALA-ARG-THR-MLY- GLN-THR-ALA-ARG- LYS

			Metals

					_ZN ×6

			Waters ×369

* Residue conservation analysis

PDB id:

3lqi

Links

Name:

Transferase

Title:

Crystal structure of mll1 phd3-bromo complexed with h3(1-9)k4me2 peptide

Structure:

Mll1 phd3-bromo. Chain: a, b, c. Fragment: third phd finger and bromodomain of mll1. Engineered: yes. Histone h3. Chain: r, s, t. Fragment: histone h3 n-terminal tail. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans.

Resolution:

1.92Å

R-factor:

0.209

R-free:

0.241

Authors:

Z.Wang,D.J.Patel

Key ref:

Z.Wang et al. (2010). Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression. Cell, 141, 1183-1194. PubMed id: 20541251

Date:

09-Feb-10

Release date:

07-Jul-10

PROCHECK

	Headers

	References

Protein chains

Q03164 (KMT2A_HUMAN) - Histone-lysine N-methyltransferase 2A from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:					3969 a.a. 176 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

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



		Enzyme reactions

Enzyme class 1:

E.C.2.1.1.- - ?????

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Enzyme class 2:

E.C.2.1.1.364 - [histone H3]-lysine(4) N-methyltransferase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

L-lysyl₄-[histone H3] + S-adenosyl-L-methionine = N₆-methyl-L- lysyl₄-[histone H3] + S-adenosyl-L-homocysteine + H⁺

L-lysyl(4)-[histone H3]	+	S-adenosyl-L-methionine	=	N(6)-methyl-L- lysyl(4)-[histone H3]	+	S-adenosyl-L-homocysteine	+	H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

Added reference

	Cell 141:1183-1194 (2010)
PubMed id: 20541251

Pro isomerization in MLL1 PHD3-bromo cassette connects H3K4me readout to CyP33 and HDAC-mediated repression.
Z.Wang, J.Song, T.A.Milne, G.G.Wang, H.Li, C.D.Allis, D.J.Patel.

ABSTRACT

The MLL1 gene is a frequent target for recurrent chromosomal translocations, resulting in transformation of hematopoietic precursors into leukemia stem cells. Here, we report on structure-function studies that elucidate molecular events in MLL1 binding of histone H3K4me3/2 marks and recruitment of the cyclophilin CyP33. CyP33 contains a PPIase and a RRM domain and regulates MLL1 function through HDAC recruitment. We find that the PPIase domain of CyP33 regulates the conformation of MLL1 through proline isomerization within the PHD3-Bromo linker, thereby disrupting the PHD3-Bromo interface and facilitating binding of the MLL1-PHD3 domain to the CyP33-RRM domain. H3K4me3/2 and CyP33-RRM target different surfaces of MLL1-PHD3 and can bind simultaneously to form a ternary complex. Furthermore, the MLL1-CyP33 interaction is required for repression of HOXA9 and HOXC8 genes in vivo. Our results highlight the role of PHD3-Bromo cassette as a regulatory platform, orchestrating MLL1 binding of H3K4me3/2 marks and cyclophilin-mediated repression through HDAC recruitment.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21404360

C.G.Kalodimos (2011).
NMR reveals novel mechanisms of protein activity regulation.

Protein Sci, 20, 773-782.

21131971

P.Sarkar, T.Saleh, S.R.Tzeng, R.B.Birge, and C.G.Kalodimos (2011).
Structural basis for regulation of the Crk signaling protein by a proline switch.

Nat Chem Biol, 7, 51-57.

PDB codes:

2l3p 2l3q 2l3s

20677349

N.McCarthy (2010).
Leukaemia: MLL makes friends and influences.

Nat Rev Cancer, 10, 529.

21164480

W.W.Tsai, Z.Wang, T.T.Yiu, K.C.Akdemir, W.Xia, S.Winter, C.Y.Tsai, X.Shi, D.Schwarzer, W.Plunkett, B.Aronow, O.Gozani, W.Fischle, M.C.Hung, D.J.Patel, and M.C.Barton (2010).
TRIM24 links a non-canonical histone signature to breast cancer.

Nature, 468, 927-932.

PDB codes:

3o33 3o34 3o35 3o36 3o37

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.