In molecular biology, the H2TH domain (helix-2turn-helix domain) is a DNA-binding

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

found in DNA glycosylase/

AP lyase The enzyme DNA-(apurinic or apyrimidinic site) lyase, also referred to as DNA-(apurinic or apyrimidinic site) 5'-phosphomonoester-lyase (systematic name) or DNA AP lyase (EC 4.2.99.18) catalyzes the cleavage of the C-O-P bond 3' from the apurinic ...

enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

, which are involved in

base excision repair Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from t ...

of DNA damaged by

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

or by mutagenic agents. Most damage to bases in DNA is repaired by the base excision repair pathway. These

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

s are primarily from bacteria, and have both DNA glycosylase activity and AP lyase activity . Examples include formamidopyrimidine-DNA glycosylases (Fpg; MutM) and

endonuclease Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain. Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (without regard to sequence), while many, typically called restriction endonucleases ...

VIII (Nei). Formamidopyrimidine-DNA glycosylases (Fpg, MutM) is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidation-damaged bases (N-glycosylase activity; ) and

cleaves Cleaves is a surname. Notable people with the surname include: * Henry B. Cleaves *Jessica Cleaves (1948–2014), American singer-songwriter *Margaret Cleaves (1848–1917), American physician *Mateen Cleaves (born 1977), American basketball player ...

both the 3'- and 5'-

phosphodiester bond In chemistry, a phosphodiester bond occurs when exactly two of the hydroxyl groups () in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. The "bond" involves this linkage . Discussion of phosphodiesters is ...

s of the resulting apurinic/apyrimidinic site (AP lyase activity;). Fpg has a preference for oxidised purines, excising oxidised purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). Its AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'- phosphates. Fpg is a

monomer In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...

composed of 2 domains connected by a flexible hinge. The two DNA-binding

motif Motif may refer to: General concepts * Motif (chess composition), an element of a move in the consideration of its purpose * Motif (folkloristics), a recurring element that creates recognizable patterns in folklore and folk-art traditions * Moti ...

s (a zinc finger and the H2TH (helix-two-turns-helix) motifs) suggest that the oxidised base is flipped out from double-stranded DNA in the binding mode and excised by a

catalytic mechanism Enzyme catalysis is the increase in the rate of a process by a biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs at a localized site, calle ...

similar to that of bifunctional base excision repair

. Fpg binds one

ion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...

at the C terminus, which contains four conserved and essential

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

s. Endonuclease VIII (Nei) has the same enzyme activities as Fpg above (,), but with a preference for oxidized pyrimidines, such as thymine glycol, 5,6- dihydrouracil and 5,6- dihydrothymine. These

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

contain three structural domains: an N-terminal catalytic core domain, a central helix-two turn-helix (H2TH) module and a C-terminal zinc finger (see PDB:1K82). The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA.

Residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applie ...

s that contact DNA are located in the catalytic domain and in a beta-hairpin

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formed by the zinc finger.

References

{{InterPro content, IPR015886 Protein domains