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Entry M0295    2.1.1.63    methylated-DNA--[protein]-cysteine S-methyltransferase

Step 01

The thiolate anion undergoes nucleophilic substitution at the methyl group, irreversibly methylating the Cys38 residue.

Rate Determining Step

This reaction is irreversible.

GIF of Reaction Step M0295.stg01


Comment: The N Ada metal coordination sphere sits at the bottom of a well in the active site. The active site environment is specific enough in shape and size to allow the methyl to approach from the Si diastereomeric face of the methylated phosphate DNA backbone group [1,4].
Spectroscopic studies have shown the sulfur to remain coordinated to the zinc centre once the reaction has occurred, even though the ability of the ligand to coordinate is reduced by the presence of the methyl group [3].
The presence of a methyl group within the Zn coordination sphere changes the tertiary structure of the enzyme sufficiently to reveal a specific DNA binding region in the N terminal region. The protein is now activated to bind onto, and increase transcription of the methylation regulon, coding for proteins involved in DNA methylation repair. The methylated form of Ada acts as a chemo-sensor for potentially mutagenic methylation within the cell [2].



Mechanisms

Bimolecular Nucleophilic Substitution

Mechanism Components

Enzyme-Substrate Bond Formation
Enzyme Not Regenerated
Bond Cleavage
Bond Formation
Overall Reactant Used
Overall Product Formed

Amino acids involved in the reaction step.

Amino Acid Location of Function Activity Function
Cys38A Side Chain reactant Activator
Attractive Charge Charge Interaction
Metal Ligand
Nucleophile

Metal Cofactors involved in Step 01

Metal Type Metal Identity Chain Activity Function
zinc ZN 93 A spectator Increase Nucleophilicity
Activator

Reactive Centre

Bonds Formed Bonds Cleaved Bonds Changed in Order Atom Types Involved
C-S
C-O
None
C
O
S

View similar reactions in MACiE.


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