PDBsum entry 3a1a

Transferase

PDB id

3a1a

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Contents

			Protein chain

					132 a.a. *

			Ligands

					EDO

			Metals

					_ZN ×3

			Waters ×17

* Residue conservation analysis

PDB id:

3a1a

Links

Name:

Transferase

Title:

Crystal structure of the dnmt3a add domain

Structure:

DNA (cytosine-5)-methyltransferase 3a. Chain: a. Fragment: add(atrx-dnmt3-dnmt3l) domain, residues 476-614. Synonym: dnmt3a, DNA methyltransferase hsaiiia, DNA mtase hsaiiia, m.Hsaiiia. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dnmt3a. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.30Å

R-factor:

0.211

R-free:

0.250

Authors:

J.Otani,K.Arita,M.Ariyoshi,M.Shirakawa

Key ref:

J.Otani et al. (2009). Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain. Embo Rep, 10, 1235-1241. PubMed id: 19834512

Date:

28-Mar-09

Release date:

10-Nov-09

PROCHECK

	Headers

	References

Protein chain

Q9Y6K1 (DNM3A_HUMAN) - DNA (cytosine-5)-methyltransferase 3A from Homo sapiens

Seq: Struc:

Seq: Struc:					912 a.a. 132 a.a.*

Key:

PfamA domain

Secondary structure

* PDB and UniProt seqs differ at 2 residue positions (black crosses)



		Enzyme reactions

Enzyme class 1:

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

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

Enzyme class 2:

E.C.2.1.1.37 - Dna (cytosine-5-)-methyltransferase.

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

Reaction:

a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-methyl- 2'-deoxycytidine in DNA + S-adenosyl-L-homocysteine + H⁺

2'-deoxycytidine in DNA	+	S-adenosyl-L-methionine	=	5-methyl- 2'-deoxycytidine in DNA	+	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

	Embo Rep 10:1235-1241 (2009)
PubMed id: 19834512

Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain.
J.Otani, T.Nankumo, K.Arita, S.Inamoto, M.Ariyoshi, M.Shirakawa.

ABSTRACT

DNMT3 proteins are de novo DNA methyltransferases that are responsible for the establishment of DNA methylation patterns in mammalian genomes. Here, we have determined the crystal structures of the ATRX-DNMT3-DNMT3L (ADD) domain of DNMT3A in an unliganded form and in a complex with the amino-terminal tail of histone H3. Combined with the results of biochemical analysis, the complex structure indicates that DNMT3A recognizes the unmethylated state of lysine 4 in histone H3. This finding indicates that the recruitment of DNMT3A onto chromatin, and thereby de novo DNA methylation, is mediated by recognition of the histone modification state by its ADD domain. Furthermore, our biochemical and nuclear magnetic resonance data show mutually exclusive binding of the ADD domain of DNMT3A and the chromodomain of heterochromatin protein 1alpha to the H3 tail. These results indicate that de novo DNA methylation by DNMT3A requires the alteration of chromatin structure.

Literature references that cite this PDB file's key reference

PubMed id

Reference

23235912

Y.Yang, and M.T.Bedford (2013).
Protein arginine methyltransferases and cancer.

Nat Rev Cancer, 13, 37-50.

23400093

Z.D.Smith, and A.Meissner (2013).
DNA methylation: roles in mammalian development.

Nat Rev Genet, 14, 204-220.

22387999

M.Stadtfeld, E.Apostolou, F.Ferrari, J.Choi, R.M.Walsh, T.Chen, S.S.Ooi, S.Y.Kim, T.H.Bestor, T.Shioda, P.J.Park, and K.Hochedlinger (2012).
Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells.

Nat Genet, 44, 398.

22231400

V.Migliori, J.Müller, S.Phalke, D.Low, M.Bezzi, W.C.Mok, S.K.Sahu, J.Gunaratne, P.Capasso, C.Bassi, V.Cecatiello, A.De Marco, W.Blackstock, V.Kuznetsov, B.Amati, M.Mapelli, and E.Guccione (2012).
Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance.

Nat Struct Mol Biol, 19, 136-144.

PDB code:

4a7j

21421568

A.Dhayalan, R.Tamas, I.Bock, A.Tattermusch, E.Dimitrova, S.Kudithipudi, S.Ragozin, and A.Jeltsch (2011).
The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9.

Hum Mol Genet, 20, 2195-2203.

20923784

K.Kashiwagi, K.Nimura, K.Ura, and Y.Kaneda (2011).
DNA methyltransferase 3b preferentially associates with condensed chromatin.

Nucleic Acids Res, 39, 874-888.

21243710

R.Z.Jurkowska, T.P.Jurkowski, and A.Jeltsch (2011).
Structure and function of mammalian DNA methyltransferases.

Chembiochem, 12, 206-222.

21666677

S.Eustermann, J.C.Yang, M.J.Law, R.Amos, L.M.Chapman, C.Jelinska, D.Garrick, D.Clynes, R.J.Gibbons, D.Rhodes, D.R.Higgs, and D.Neuhaus (2011).
Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin.

Nat Struct Mol Biol, 18, 777-782.

PDB code:

2lbm

21666679

S.Iwase, B.Xiang, S.Ghosh, T.Ren, P.W.Lewis, J.C.Cochrane, C.D.Allis, D.J.Picketts, D.J.Patel, H.Li, and Y.Shi (2011).
ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome.

Nat Struct Mol Biol, 18, 769-776.

PDB codes:

3ql9 3qla 3qlc 3qln

21243717

S.S.Oliver, and J.M.Denu (2011).
Dynamic interplay between histone H3 modifications and protein interpreters: emerging evidence for a "histone language".

Chembiochem, 12, 299-307.

21304883

S.Sharma, D.D.De Carvalho, S.Jeong, P.A.Jones, and G.Liang (2011).
Nucleosomes containing methylated DNA stabilize DNA methyltransferases 3A/3B and ensure faithful epigenetic inheritance.

PLoS Genet, 7, e1001286.

21321601

X.J.He, T.Chen, and J.K.Zhu (2011).
Regulation and function of DNA methylation in plants and animals.

Cell Res, 21, 442-465.

20838592

B.L.Wienholz, M.S.Kareta, A.H.Moarefi, C.A.Gordon, P.A.Ginno, and F.Chédin (2010).
DNMT3L modulates significant and distinct flanking sequence preference for DNA methylation by DNMT3A and DNMT3B in vivo.

PLoS Genet, 6, 0.

21124827

D.H.Lee, P.Singh, S.Y.Tsai, N.Oates, A.Spalla, C.Spalla, L.Brown, G.Rivas, G.Larson, T.A.Rauch, G.P.Pfeifer, and P.E.Szabó (2010).
CTCF-dependent chromatin bias constitutes transient epigenetic memory of the mother at the H19-Igf2 imprinting control region in prospermatogonia.

PLoS Genet, 6, e1001224.

21339843

H.Hashimoto, P.M.Vertino, and X.Cheng (2010).
Molecular coupling of DNA methylation and histone methylation.

Epigenomics, 2, 657-669.

20651149

H.Wu, V.Coskun, J.Tao, W.Xie, W.Ge, K.Yoshikawa, E.Li, Y.Zhang, and Y.E.Sun (2010).
Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes.

Science, 329, 444-448.

20142834

J.A.Law, and S.E.Jacobsen (2010).
Establishing, maintaining and modifying DNA methylation patterns in plants and animals.

Nat Rev Genet, 11, 204-220.

20651253

P.W.Lewis, S.J.Elsaesser, K.M.Noh, S.C.Stadler, and C.D.Allis (2010).
Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres.

Proc Natl Acad Sci U S A, 107, 14075-14080.

20147399

V.Lukashchuk, and R.D.Everett (2010).
Regulation of ICP0-null mutant herpes simplex virus type 1 infection by ND10 components ATRX and hDaxx.

J Virol, 84, 4026-4040.

20210320

X.Cheng, and R.M.Blumenthal (2010).
Coordinated chromatin control: structural and functional linkage of DNA and histone methylation.

Biochemistry, 49, 2999-3008.

20223770

Y.Zhang, R.Jurkowska, S.Soeroes, A.Rajavelu, A.Dhayalan, I.Bock, P.Rathert, O.Brandt, R.Reinhardt, W.Fischle, and A.Jeltsch (2010).
Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail.

Nucleic Acids Res, 38, 4246-4253.

20048137

C.A.Musselman, and T.G.Kutateladze (2009).
PHD fingers: epigenetic effectors and potential drug targets.

Mol Interv, 9, 314-323.

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 code is shown on the right.