Escherichia coli Migula (bacterium) K-12 MG1655 [ECO]

FULL NAME: Methylphosphotriester-DNA--protein-cysteine S-methyltransferase


DESCRIPTION:
The methylation of Ada by methylphosphotriesters in DNA leads to its activation as a transcriptional regulator that activates the transcription of its own gene, ada, and other alkylation resistance genes, alkA, alkB and aidB. Is involved in the adaptive response to alkylation damage in DNA caused by alkylating agents. Repairs O6-methylguanine and 04-methylthymine residues in alkylated DNA by a direct and irreversible transfer of the methyl group from the base to one of its own cysteine residues (Cys-321). Also specifically repairs the Sp diastereomer of DNA methylphosphotriester lesions by the same mechanism, although the methyl transfer occurs onto a different cysteine residue (Cys-38). Can not demethylate the other diastereomer, Rp-methylphosphotriester.

MISCELLANEOUS:
This enzyme catalyzes only one turnover and therefore is not strictly catalytic. According to one definition, an enzyme is a biocytalyst that acts repeatedly and over many reaction cycles.


STRUCTURE SIMILARITY:
In the C-terminal section; belongs to the MGMT family.
Contains 1 HTH araC/xylS-type DNA-binding domain.


SUBUNIT STRUCTURE:
Consists of two domains. The 20 kDa N-terminal domain repairs the Sp diastereomer of methylphosphotriesters and, in its methylated form, binds DNA in a sequence-specific manner. The 19 kDa C-terminal domain repairs the mutagenic lesions O6-methylguanine. Each domain retains its activity when separated form the other.


CATALYTIC ACTIVITY:
DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine.
DNA (containing Sp-methylphosphotriester) + protein L-cysteine = DNA (without Sp-methylphosphotriester) + protein S-methyl-L-cysteine.


ENZYME REGULATION:
Up-regulated by methylated Ada itself in response to the exposure to alkylating agents.


RELATED PATHWAY(S):
direct reversal (DR)


RELATED DAMAGE:
O6-methyl G (O6meG)
MePT
O4-methyl T (O4meT)


Amino acids sequence

        10         20         30         40         50         60
MKKATCLTDD QRWQSVLARD PNADGEFVFA VRTTGIFCRP SCRARHALRE NVSFYANASE
        70         80         90        100        110        120
ALAAGFRPCK RCQPEKANAQ QHRLDKITHA CRLLEQETPV TLEALADQVA MSPFHLHRLF
       130        140        150        160        170        180
KATTGMTPKA WQQAWRARRL RESLAKGESV TTSILNAGFP DSSSYYRKAD ETLGMTAKQF
       190        200        210        220        230        240
RHGGENLAVR YALADCELGR CLVAESERGI CAILLGDDDA TLISELQQMF PAADNAPADL
       250        260        270        280        290        300
MFQQHVREVI ASLNQRDTPL TLPLDIRGTA FQQQVWQALR TIPCGETVSY QQLANAIGKP
       310        320        330        340        350
KAVRAVASAC AANKLAIIIP CHRVVRGDGT LSGYRWGVSR KAQLLRREAE NEER

Encoded by ada gene


OTHER NAME(S):
ECK2205
JW2201


DESCRIPTION:
The Ada N-terminal domain acts as a transcriptional activator of ada, alkA, alkB and aidB. [More information is available at EcoGene: EG10029]. O6-methylguanine and O4-methylthymine are the major mutagenic lesions resulting from exposure of DNA to simple alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-methyl-N-nitrosourea (MNU) and, to a lesser degree, methane methanesulfonate (MMS). [More information is available at EcoCyc: EG10029].


Nucleic acid sequence

        10         20         30         40         50         60
atgaaaaaag ccacatgctt aactgacgat caacgctggc aatctgtctt agcccgcgac
        70         80         90        100        110        120
ccgaatgccg acggcgaatt cgttttcgcc gtgcgtacca caggcatctt ttgccgtccg
       130        140        150        160        170        180
tcttgccgcg ccagacatgc tttgcgggaa aacgtctcct tctacgcaaa tgccagcgag
       190        200        210        220        230        240
gcactcgccg ctggctttcg cccctgcaaa cgttgtcagc cagaaaaagc caatgcccag
       250        260        270        280        290        300
caacatcggt tggataaaat cacccacgcg tgtcgactgc tggaacagga aacgcctgta
       310        320        330        340        350        360
acgctggaag ccttagccga ccaggtggcg atgagtccat ttcatctaca tcggttgttt
       370        380        390        400        410        420
aaagcgacta ccggaatgac gcctaaagcc tggcaacagg cctggcgcgc tcgccgtttg
       430        440        450        460        470        480
cgcgaatcgc tggcgaaagg ggagagcgtg acgacgtcta ttcttaacgc cggattcccc
       490        500        510        520        530        540
gacagcagca gttactatcg caaagctgac gaaacgctgg gcatgacggc taaacaattc
       550        560        570        580        590        600
cgtcacggtg gcgaaaatct ggcggtgcgt tacgcgctgg ctgattgtga gctgggtcgt
       610        620        630        640        650        660
tgcctggtgg cagaaagcga gcgggggatt tgcgcgatat tgctgggcga tgatgacgcg
       670        680        690        700        710        720
acactaatca gcgagttgca gcagatgttt cccgctgccg acaacgcgcc tgccgatctg
       730        740        750        760        770        780
atgtttcagc aacatgtgcg tgaagtgatc gccagcctca atcaacgcga tacgccgctg
       790        800        810        820        830        840
acgttaccgc tggacattcg cggcactgct tttcagcaac aagtctggca ggcactgcgc
       850        860        870        880        890        900
acgatacctt gcggtgaaac cgtcagttat cagcaactgg ctaacgccat cggcaaaccg
       910        920        930        940        950        960
aaagcggtac gggccgttgc cagcgcctgt gccgccaaca agctggctat cataataccc
       970        980        990       1000       1010       1020
tgtcatcggg tggtccgtgg tgatggcaca ctttccggtt accgctgggg cgtgtcgcgt
      1030       1040       1050       1060
aaagcgcaac tgctgcgccg cgaagctgaa aatgaggaga ggtaa 

Last modification date: Oct. 6, 2011