Page last updated: 2024-10-24

methylated-DNA-[protein]-cysteine S-methyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: DNA (containing 6-O-methylguanine) + (protein)-L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine. [EC:2.1.1.63]

Methylated-DNA-[protein]-cysteine S-methyltransferase activity is a specialized enzymatic function that involves the transfer of a methyl group from a donor molecule, such as S-adenosyl methionine (SAM), to a cysteine residue within a protein that is bound to methylated DNA. This reaction typically occurs within the context of a larger protein complex, where the methyltransferase enzyme interacts with both the DNA and the target protein. The specific role of this methylation event varies depending on the protein and the DNA sequence involved, but generally, it serves to modulate protein-DNA interactions, influencing processes such as gene regulation, DNA repair, and chromatin structure.

The process begins with the binding of the methyltransferase enzyme to a methylated DNA sequence. This binding event is often mediated by specific protein domains that recognize the methylated cytosine bases within the DNA. Once bound, the enzyme positions the target protein, which is also bound to the methylated DNA, in close proximity to the active site of the methyltransferase. This positioning allows for the efficient transfer of a methyl group from SAM to the cysteine residue within the target protein.

The methylation reaction itself is a complex process that involves a series of conformational changes within the enzyme and the target protein. These changes are essential for ensuring the correct positioning of the reactants and for facilitating the transfer of the methyl group. Upon completion of the methylation event, the methylated protein is released from the enzyme, and the enzyme can then bind to another target protein.

The methylation of a cysteine residue within a protein bound to methylated DNA can have a profound impact on the protein's activity and its interactions with other molecules. In some cases, methylation can increase the affinity of the protein for DNA, leading to enhanced gene expression. In other cases, methylation can reduce the protein's affinity for DNA, leading to gene repression. Methylation can also influence the protein's interactions with other proteins, affecting the formation of regulatory complexes and signaling pathways.

Overall, methylated-DNA-[protein]-cysteine S-methyltransferase activity is a critical regulatory mechanism that plays a vital role in a wide range of cellular processes. This enzymatic activity is essential for maintaining the proper balance of gene expression, DNA repair, and chromatin structure, and it is implicated in a number of diseases, including cancer and neurodevelopmental disorders.'
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Proteins (1)

ProteinDefinitionTaxonomy
Methylated-DNA--protein-cysteine methyltransferaseA methylated-DNA--protein-cysteine methyltransferase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P16455]Homo sapiens (human)

Compounds (8)

CompoundDefinitionClassesRoles
nu2058NU2058: structure in first source
o(6)-benzylguanineO(6)-benzylguanine: a suicide inhibitor of O(6)-methylguanine-DNA methyltransferase activity
o-(6)-methylguanine6-O-methylguanine : A methylguanine in which the methyl group is positioned on the oxygen at position 6. Formed in DNA by alkylation of the oxygen atom of guanine, most often by N-nitroso compounds and sometimes due to methylation by other compounds such as endogenous S-adenosylmethionine, it base-pairs to thymine rather than cytidine, causing a G:C to A:T transition in DNA.

methylguanine : A 2-aminopurine that is guanine bearing a single methyl substituent.

O-(6)-methylguanine: structure
methylguaninemutagen
o(6)-n-butylguanine
6-ethylguanine6-ethylguanine: found in rat brain DNA
o(6)-benzyl-2'-deoxyguanosine
2,4-diamino-6-benzyloxy-5-nitrosopyrimidine2,4-diamino-6-benzyloxy-5-nitrosopyrimidine: inhibits O(6)-alkylguanine-DNA alkyltransferase; structure given in first source
lomeguatrib