Ada (protein)
Ada, also called as ''O''6 alkyl guanine transferase I (''O''6 AGT I), is an enzyme induced by treatment of ''E. coli'' cells with alkylating agents that mainly cause methylation damage. This phenomenon is called the adaptive response hence the name. Ada transfers the alkyl group from DNA bases and sugar-phosphate backbone to a cysteine residue, inactivating itself. Consequently, it reacts stoichiometrically with its substrate rather than catalytically and is referred to as a suicide enzyme. Methylation of Ada protein converts it into a self transcriptional activator, inducing its own gene expression and the expression of other genes which together with Ada help the cells repair alkylation damage. Ada removes the alkyl group attached to DNA bases like guanine (O6-alkyl guanine) or thymine (O4-alkyl thymine) and to the oxygen of the phosphodiester backbone of the DNA. However, Ada shows greater preference for O6- alkyl guanine compared to either O4-thymine and alkylated phosphotrie ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecules known as product (chemistry), products. Almost all metabolism, metabolic processes in the cell (biology), cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme, pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts include Ribozyme, catalytic RNA molecules, also called ribozymes. They are sometimes descr ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Alkylating Agents
Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting alkylation. Alkyl groups can also be removed in a process known as dealkylation. Alkylating agents are often classified according to their nucleophilic or electrophilic character. In oil refining contexts, alkylation refers to a particular alkylation of isobutane with olefins. For upgrading of petroleum, alkylation produces a premium blending stock for gasoline. In medicine, alkylation of DNA is used in chemotherapy to damage the DNA of cancer cells. Alkylation is accomplished with the class of drugs called alkylating antineoplastic agents. Nucleophilic alkylating agents Nucleophilic alkylating agents deliver the equivalent of an alkyl anion ( carbanion). The formal "alkyl anion" attacks an electrophile, forming a new covalent bond ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Methylation
Methylation, in the chemistry, chemical sciences, is the addition of a methyl group on a substrate (chemistry), substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen#Compounds, hydrogen atom. These terms are commonly used in chemistry, biochemistry, soil science, and biology. In biological systems, methylation is Catalysis, catalyzed by enzymes; such methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of Protein#Functions, protein function, and RNA processing. ''In vitro'' methylation of tissue samples is also a way to reduce some histology#Histological Artifacts, histological staining artifacts. The reverse of methylation is demethylation. In biology In biological systems, methylation is accomplished by enzymes. Methylation can modify heavy metals and can regulate gene expression, RNA processing, and protein function. It is a key pro ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Adaptive Response
The adaptive response is a DNA damage response pathway prevalent across bacteria that protects DNA from damage by external agents or by errors during replication.Landini, P, Volkert MR. (2000Regulatory Responses of the Adaptive Response to Alkylation Damage: a Simple Regulon with Complex Regulatory Features''J. Bacteriol.'' 182(23): 6543–6549. It is initiated specifically against alkylation, particularly methylation, of guanine or thymine nucleotides or phosphate groups on the sugar-phosphate backbone of DNA. Under sustained exposure to low-level treatment with alkylating mutagens, bacteria can adapt to the presence of the mutagen, rendering subsequent treatment with high doses of the same agent less effective.Volkert MR. (1988)Adaptive response of ''Escherichia coli'' to alkylation damage.''Environ Mol Mutagen'' 11(2):241-55. Function Environmental influence plays a crucial role in the developmental plasticity of genotypes due to the introduction of DNA damaging agents. This p ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Stoichiometrically
Stoichiometry () is the relationships between the masses of reactants and products before, during, and following chemical reactions. Stoichiometry is based on the law of conservation of mass; the total mass of reactants must equal the total mass of products, so the relationship between reactants and products must form a ratio of positive integers. This means that if the amounts of the separate reactants are known, then the amount of the product can be calculated. Conversely, if one reactant has a known quantity and the quantity of the products can be empirically determined, then the amount of the other reactants can also be calculated. This is illustrated in the image here, where the unbalanced equation is: : : However, the current equation is imbalanced. The reactants have 4 hydrogen and 2 oxygen atoms, while the product has 2 hydrogen and 3 oxygen. To balance the hydrogen, a coefficient of 2 is added to the product H2O, and to fix the imbalance of oxygen, it is also added to ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Guanine
Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called guanosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine- imidazole ring system with conjugated double bonds. This unsaturated arrangement means the bicyclic molecule is planar. Properties Guanine, along with adenine and cytosine, is present in both DNA and RNA, whereas thymine is usually seen only in DNA, and uracil only in RNA. Guanine has multiple tautomeric forms. For the imidazole ring, the proton can reside on either nitrogen. For the pyrimidine ring, the ring N-H can center can reside on either of the ring nitrogens. The latter tautomer does not apply to nucleoside or nucleotide versions of guanine. It binds to cytosine through three hydrogen bonds. In cytosine, t ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Thymine
Thymine () (symbol T or Thy) is one of the four nucleotide bases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. In RNA, thymine is replaced by the nucleobase uracil. Thymine was first isolated in 1893 by Albrecht Kossel and Albert Neumann from calf thymus glands, hence its name. Derivation As its alternate name (5-methyluracil) suggests, thymine may be derived by methylation of uracil at the 5th carbon. In RNA, thymine is replaced with uracil in most cases. In DNA, thymine (T) binds to adenine (A) via two hydrogen bonds, thereby stabilizing the nucleic acid structures. Thymine combined with deoxyribose creates the nucleoside deoxythymidine, which is synonymous with the term thymidine. Thymidine can be phosphorylated with up to three phosphoric acid groups, producing dTMP (deoxythymidine monophosphate), dTDP, or dTTP (for the ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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AGT II
''O''6-alkylguanine DNA alkyltransferase II (''O''6 AGT II) previously known as ''O''6 Guanine transferase (ogt) is an ''E. coli'' protein that is involved in DNA repair together with Ada ( also known as ''O''6 AGT I). Like AGT I, AGT II is responsible for the removal of alkyl groups from ''O''6-alkyl guanine, ''O''4-alkyl thymine and alkyl phosphotriester in the sugar-phosphate backbone of DNA. AGT II shows a greater preference for ''O''4-alkyl thymine than ''O''6-alkyl guanine and alkyl phosphotriester. Unlike Ada, AGT II is expressed constitutively in cells. Therefore, AGT II will repair alkylated DNA adduct In molecular genetics, a DNA adduct is a segment of DNA bound to a Carcinogen, cancer-causing chemical. This process could lead to the development of cancerous cells, or carcinogenesis. DNA adducts in scientific experiments are used as biomarkers ...s even before Ada is fully induced. AGT II is similar to Ada in its suicide inactivation in that AGT II transfers the a ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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O-6-methylguanine-DNA Methyltransferase
Methylated-DNA--protein-cysteine methyltransferase (MGMT), also known as ''O''6-alkylguanine DNA alkyltransferase AGT, is a protein that in humans is encoded by the ''MGMT'' gene. MGMT is crucial for genome stability. It repairs the naturally occurring mutagenic DNA lesion O6-methylguanine back to guanine and prevents mismatch and errors during DNA replication and transcription. Accordingly, loss of ''MGMT'' increases the carcinogenic risk in mice after exposure to alkylating agents. The two bacterial isozymes are Ada and Ogt. Function and mechanism Although alkylating mutagens preferentially modify the guanine base at the N7 position, ''O''6-alkyl-guanine is a major carcinogenic lesion in DNA. This DNA adduct is removed by the repair protein ''O''6-alkylguanine DNA alkyltransferase through an SN2 mechanism. This protein is not a true enzyme since it removes the alkyl group from the lesion in a stoichiometric reaction and the active enzyme is not regenerated after it is ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Transferases
In biochemistry, a transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl group, methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of different Molecular pathway, biochemical pathways throughout biology, and are integral to some of life's most important processes. Transferases are involved in myriad reactions in the cell. Three examples of these reactions are the activity of coenzyme A (CoA) Coenzyme A transferases, transferase, which transfers Thioester, thiol esters, the action of N-acetyltransferase, which is part of the pathway that metabolizes tryptophan, and the regulation of pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl CoA. Transferases are also utilized during translation. In this case, an amino acid chain is the functional group transferred by a peptidyl transferase. The transfer involves the removal of the growing ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |