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Overview for MACiE Entry M0293

Version history

General Information

EC Number: 2.1.1.37 (A member of the Transferases, Transferring one-carbon groups, Methyltransferases)

Enzyme Name: cytosine-specific methyltransferase HhaI

Biological Species: Haemophilus parahaemolyticus (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P05102 - Modification methylase HhaI

Representative PDB Code: 1mht - COVALENT TERNARY STRUCTURE OF HHAI METHYLTRANSFERASE, DNAAND S-ADENOSYL-L-HOMOCYSTEINE (Resolution = 2.60 Å).

Catalytic CATH Codes:

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of DNA cytosine

Image of S-adenosyl-L-methionine

right arrow

Image of DNA 5-methylcytosine

Image of S-adenosyl-L-homocysteine

DNA cytosine
C00856
S-adenosyl-L-methionine
C00019
CHEBI:59789
DNA 5-methylcytosine
C02967
S-adenosyl-L-homocysteine
C00021
CHEBI:57856

This reaction is irreversible.

Overall Comment: The ring of cytosine is delivered to the active site by "flipping" the base out of the helix and replacing inter-helix hydrogen bond interactions with protein-helix interactions [1,3]. There is uncertainty in the literature as to the specific role of Glu119. In this annotation, the residue is shown to promote a resonance structure which enhances the electrophilicity at the C6 position of the cytosine ring, rather than acting a a general acid during the reaction [4].


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Stepwise Description of the Reaction

Step 1The catalytic Cys81 is deprotonated by the substrate-cofactor DNA phosphate group.
Step 2The cystine thiolate attacks at the C6 position of the cytosine ring.
Step 3The carbanion residing on C5 attacks the methyl group of SAM. This results in methylation of the cytosine ring.
Step 4Elimination of the Cys81 side chain involves interactions with a bridging water molecule which facilitates the elimination of the syn related proton, leaving a double bond.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Cys 81 A Side Chain
Arg 163 A Side Chain
Arg 165 A Side Chain
Glu 119 A Side Chain

References

  1. S. Klimasauskas et al. (1997), Cell, 76, 357-369. HhaI methyltransferase flips its target base out of the DNA helix.
    Medline: 8293469
  2. G. Vilkaitis et al. (2001), J. Biol. Chem., 276, 20924-20934. The mechanism of DNA cytosine-5 methylation. Kinetic and mutational dissection of Hhai methyltransferase.
    Medline: 11283006
  3. D. A. Erlanson et al. (1993), J. Am. Chem. Soc., 115, 12583-12584. DNA Methylation through a Locally Unpaired Intermediate.
  4. R. Zangi et al. (2010), J. Mol. Biol., 400, 632-644. Mechanism of DNA methylation: the double role of DNA as a substrate and as a cofactor.
    Medline: 2047198

Homologue information for M0293 (1mht)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0046 site-specific DNA-methyltransferase
2.1.1.72
2adm 3.40.50.150
0.04160Compare

Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

GOA logo
DNA binding (molecular function)
DNA (cytosine-5-)-methyltransferase activity (molecular function)
DNA methylation (biological process)
methyltransferase activity (molecular function)
DNA restriction-modification system (biological process)
transferase activity (molecular function)
methylation (biological process)
C-5 methylation of cytosine (biological process)
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