DNA (cytosine-5-)-methyltransferase activity
Definition
Target type: molecularfunction
Catalysis of the reaction: S-adenosyl-L-methionine + DNA containing cytosine = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine. [EC:2.1.1.37]
DNA (cytosine-5-)-methyltransferase activity refers to the enzymatic ability of certain proteins to catalyze the transfer of a methyl group from a donor molecule, typically S-adenosyl methionine (SAM), to the 5' position of cytosine bases within DNA. This methylation process is crucial for various cellular functions, including gene regulation, genomic imprinting, and DNA replication.
The molecular mechanism of DNA methylation by these enzymes involves several key steps:
1. **Substrate Binding:** The methyltransferase recognizes and binds to specific DNA sequences, typically CpG dinucleotides, where a cytosine base is followed by a guanine base.
2. **SAM Binding:** The enzyme binds to the methyl donor, SAM, positioning the methyl group in proximity to the target cytosine.
3. **Catalytic Activity:** The methyltransferase facilitates the transfer of the methyl group from SAM to the 5' position of the cytosine base, forming 5-methylcytosine (5mC).
4. **Product Release:** After methylation, the enzyme releases the modified DNA and the demethylated SAM molecule.
This methylation event can have profound effects on gene expression. Methylated cytosines are typically associated with silenced genes, while unmethylated cytosines are often found in active genes. This is due to the ability of methylated DNA to interact with specific proteins, such as methyl-CpG binding proteins (MBPs), that can recruit repressive chromatin remodeling complexes.
Moreover, DNA methylation plays a role in genomic imprinting, where the expression of certain genes is determined by the parental origin of the chromosome. This process involves differential methylation patterns in the germline, which are inherited by offspring.
Furthermore, DNA methylation is involved in DNA replication by regulating the activity of replication origins.
The dysregulation of DNA (cytosine-5-)-methyltransferase activity has been implicated in various diseases, including cancer, cardiovascular disease, and neurological disorders.'
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| DNA (cytosine-5)-methyltransferase 3A | A DNA (cytosine-5)-methyltransferase 3A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y6K1] | Homo sapiens (human) |
| DNA (cytosine-5)-methyltransferase 3B | A DNA (cytosine-5)-methyltransferase 3B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UBC3] | Homo sapiens (human) |
| DNA (cytosine-5)-methyltransferase 1 | A DNA (cytosine-5)-methyltransferase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P26358] | Homo sapiens (human) |
Compounds (22)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| procainamide | procainamide : A benzamide that is 4-aminobenzamide substituted on the amide N by a 2-(diethylamino)ethyl group. It is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias. Procainamide: A class Ia antiarrhythmic drug that is structurally-related to PROCAINE. | benzamides | anti-arrhythmia drug; platelet aggregation inhibitor; sodium channel blocker |
| vorinostat | vorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL). Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME. | dicarboxylic acid diamide; hydroxamic acid | antineoplastic agent; apoptosis inducer; EC 3.5.1.98 (histone deacetylase) inhibitor |
| dichlone | dichlone: structure | ||
| azacitidine | 5-azacytidine : An N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via an N-glycosidic linkage. An antineoplastic agent, it is used in the treatment of myeloid leukaemia. Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent. | N-glycosyl-1,3,5-triazine; nucleoside analogue | antineoplastic agent |
| epigallocatechin gallate | (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin. epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis) | flavans; gallate ester; polyphenol | antineoplastic agent; antioxidant; apoptosis inducer; geroprotector; Hsp90 inhibitor; neuroprotective agent; plant metabolite |
| 5,5'-methylenedisalicylic acid | 5,5'-methylenedisalicylic acid: inhibits attachment of ribosomes to microsomal membranes; RN given refers to parent cpd; structure in first source & Merck Index, 9th ed, #5934 | ||
| s-tubercidinylhomocysteine | |||
| 6-bromo-3-(bromomethyl)-7-methyl-2,3,7-trichloro-1-octene | 6-bromo-3-(bromomethyl)-7-methyl-2,3,7-trichloro-1-octene: structure given in first source | monoterpenoid; organobromine compound; organochlorine compound | algal metabolite; antineoplastic agent; marine metabolite |
| s-adenosyl-3-thiopropylamine | S-adenosyl-3-thiopropylamine : A thioadenosine that is adenosine in which the hydroxy group at C-5' is replaced by a 3-aminopropyl group. S-adenosyl-3-thiopropylamine: decarboxylated S-adenosylhomocysteine; RN given refers to parent cpd | organic sulfide; primary amino compound; thioadenosine | |
| n(4)-adenosyl-n(4)-methyl-2,4-diaminobutanoic acid | |||
| nsc 401077 | NSC 401077: inhibits DNA methyltransferase DNMT1; structure in first source | ||
| s-adenosylhomocysteine | S-adenosyl-L-homocysteine : An organic sulfide that is the S-adenosyl derivative of L-homocysteine. S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions. | adenosines; amino acid zwitterion; homocysteine derivative; homocysteines; organic sulfide | cofactor; EC 2.1.1.72 [site-specific DNA-methyltransferase (adenine-specific)] inhibitor; EC 2.1.1.79 (cyclopropane-fatty-acyl-phospholipid synthase) inhibitor; epitope; fundamental metabolite |
| nanaomycin a | nanaomycin A : A pyranonaphthoquinone antibiotic from strain OS-3966 of Streptomyces rosa var. notoensis. nanaomycin A: produced by a strain OS-3966 of Streptomyces rosa var. notoensis; quinone-related cpd; MF C16-H14-O6; see also nanaomycin B: 52934-85-7, nanaomycin C: 58286-55-8, nanaomycin E: 72660-52-7; structure | benzoisochromanequinone; monocarboxylic acid; organooxygen heterocyclic antibiotic; p-quinones | bacterial metabolite |
| decitabine | 2'-deoxyribonucleoside | ||
| rg108 | RG108: DNA methyltransferase inhibitor; structure in first source | indolyl carboxylic acid | |
| genistein | 7-hydroxyisoflavones | antineoplastic agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; geroprotector; human urinary metabolite; phytoestrogen; plant metabolite; tyrosine kinase inhibitor | |
| psammaplin a | psammaplin A: isolated from marine sponges Poecillastra and Jaspis; structure in second source | ||
| sgi-1027 | SGI-1027: inhibits DNA methyltransferase 1; structure in first source | ||
| bix 01294 | piperidines | ||
| unc 0638 | UNC 0638: inhibits lysine methyltransferases G9a and GLP; structure in first source | quinazolines | |
| gsk343 | GSK343 : A member of the class of indazoles that is 1-isopropyl-1H-indazole-4-carboxamide in which the nitrogen of the carboxamide group is substituted by a (6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl group and in which the indazole ring is substituted at position 6 by a 2-(4-methylpiperazin-1-yl)pyridin-4-yl group. A highly potent and selective EZH2 inhibitor (IC50 = 4 nM). GSK343: an EZH2 methyltransferase inhibitor | aminopyridine; indazoles; N-alkylpiperazine; N-arylpiperazine; pyridone; secondary carboxamide | antineoplastic agent; apoptosis inducer; EC 2.1.1.43 (enhancer of zeste homolog 2) inhibitor |
| 6,7-dimethoxy-2-(pyrrolidin-1-yl)-n-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine | 6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine: a SETD8 inhibitor; structure in first source |