PDBsum entry 3av6

Transferase

PDB id: 3av6

Contents

Protein chain

1135 a.a.

Ligands

SAM

Metals

_ZN ×4

PDB id:

3av6

Name:

Transferase

Title:

Crystal structure of mouse DNA methyltransferase 1 with adomet

Structure:

DNA (cytosine-5)-methyltransferase 1. Chain: a. Fragment: unp residues 291-1620. Synonym: dnmt1, met-1, DNA methyltransferase mmui, DNA mtase mmui, m.Mmui, mcmt. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: dnmt1, dnmt, met1, uim. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

3.09Å R-factor: 0.195 R-free: 0.255

Authors:

K.Takeshita,I.Suetake,E.Yamashita,M.Suga,H.Narita,A.Nakagawa,S.Tajima

Key ref:

K.Takeshita et al. (2011). Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1). Proc Natl Acad Sci U S A, 108, 9055-9059. PubMed id: 21518897

Date:

22-Feb-11 Release date: 04-May-11

Protein chain

P13864  (DNMT1_MOUSE) -  DNA (cytosine-5)-methyltransferase 1 from Mus musculus

Seq: 1620 a.a.

Struc: 1135 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.1.37 - Dna (cytosine-5-)-methyltransferase.
• 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 (Bound ligand (Het Group name = SAM) corresponds exactly) = 5-methyl- 2'-deoxycytidine in DNA + S-adenosyl-L-homocysteine + H(+)

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

Added reference

Proc Natl Acad Sci U S A 108:9055-9059 (2011)

PubMed id: 21518897

Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).

K.Takeshita, I.Suetake, E.Yamashita, M.Suga, H.Narita, A.Nakagawa, S.Tajima.

ABSTRACT

Methylation of cytosine in DNA plays a crucial role in development through inheritable gene silencing. The DNA methyltransferase Dnmt1 is responsible for the propagation of methylation patterns to the next generation via its preferential methylation of hemimethylated CpG sites in the genome; however, how Dnmt1 maintains methylation patterns is not fully understood. Here we report the crystal structure of the large fragment (291-1620) of mouse Dnmt1 and its complexes with cofactor S-adenosyl-L-methionine and its product S-adenosyl-L-homocystein. Notably, in the absence of DNA, the N-terminal domain responsible for targeting Dnmt1 to replication foci is inserted into the DNA-binding pocket, indicating that this domain must be removed for methylation to occur. Upon binding of S-adenosyl-L-methionine, the catalytic cysteine residue undergoes a conformation transition to a catalytically competent position. For the recognition of hemimethylated DNA, Dnmt1 is expected to utilize a target recognition domain that overhangs the putative DNA-binding pocket. Taking into considerations the recent report of a shorter fragment structure of Dnmt1 that the CXXC motif positions itself in the catalytic pocket and prevents aberrant de novo methylation, we propose that maintenance methylation is a multistep process accompanied by structural changes.