Overview for MACiE Entry M0293
EC Number: 220.127.116.11 (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
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 .
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Stepwise Description of the Reaction
|Step 1||The catalytic Cys81 is deprotonated by the substrate-cofactor DNA phosphate group.|
|Step 2||The cystine thiolate attacks at the C6 position of the cytosine ring.|
|Step 3||The carbanion residing on C5 attacks the methyl group of SAM. This results in methylation of the cytosine ring.|
|Step 4||Elimination 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.|
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Catalytic Residues Involved
||Location of Function
- S. Klimasauskas et al. (1997), Cell, 76, 357-369. HhaI methyltransferase flips its target base out of the DNA helix.
- 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.
- D. A. Erlanson et al. (1993), J. Am. Chem. Soc., 115, 12583-12584. DNA Methylation through a Locally Unpaired Intermediate.
- 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.
Homologue information for M0293 (1mht)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
Entries with at least one Catalytic CATH code in common (different mechanisms):
|M0046 ||site-specific DNA-methyltransferase |
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