AlkB
Encyclopedia
AlkB protein is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 induced during an adaptive response
Adaptive response
The adaptive response is a form of direct DNA repair in E. coli that is initiated 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, E...

 and is involved in the direct reversal of alkylation
Alkylation
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion or a carbene . Alkylating agents are widely used in chemistry because the alkyl group is probably the most common group encountered in...

 damage [1]. AlkB specifically removes alkylation damage to single stranded (SS) DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 caused by SN2 type of chemical agents [2]. It efficiently removes methyl groups from 1-methyl adenines, 3-methyl cytosines in SS DNA [1,3]. AlkB belongs to the Fe (II)/2-oxoglutarate-dependent dioxygenase superfamily and oxidatively demethylates the DNA substrate [1,3]. Demethylation
Demethylation
Demethylation is the chemical process resulting in the removal a of methyl group from a molecule.A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms....

by AlkB is accompanied with release of CO2, succinate and formaldehyde [3].

Human homologs

There are eight human homologs of AlkB, of which, only ABH2 and ABH3 [1] have known function. They are:
, , , , , , ,

ABH3, like E. coli AlkB, is specific for SS DNA and RNA [1] whereas ABH2 has higher affinity for damages in double-stranded DNA [4].

There is also another very different protein called AlkB or alkane hydroxylase. It is the catalytic subunit of a non-heme diiron protein, catalyzing the hydroxylation of alkanes, in aerobic bacteria that are able to utilize alkanes as a carbon source.

Functions

AlkB has since been shown to have an ever expanding range of substrates since its initial discovery by Sedgwick, Lindahl, and Seeberg. Not only does it remove alkylation damage from the positively charged 1-methyl adenines and 3-methyl cytosines, but also from the neutral bases of 1-methyl guanine and 3-methyl thymine[5]. AlkB has been shown as the first example of a DNA repair enzyme converting one type of DNA damage that blocks DNA replication, to another type of damage that the DNA polymerase can traverse with ease. This was seen for the cyclic lesion ethanoadenine (not to be confused with ethenoadenine...see below), which upon hydroxylation by AlkB, affords an N6-acetaldehyde lesion, thus affording an 'adenine' hydrogen-bonding face[6]. In contrast to the previous types of alkylation damage removed by AlkB via a hydroxylation mechanism, AlkB has been shown to epoxidize the double bond of ethenoadenine, which is hydrolyzed to a diol, and ultimately released as the dialdehyde glyoxal, thus restoring the undamaged adenine in the DNA[7].
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