{PDOC00598}
{PS00726; AP_NUCLEASE_F1_1}
{PS00727; AP_NUCLEASE_F1_2}
{PS00728; AP_NUCLEASE_F1_3}
{PS51435; AP_NUCLEASE_F1_4}
{BEGIN}
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* AP endonucleases family 1 signatures and profile *
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Cellular DNA is spontaneously and continuously damaged by environmental and
internal factors such as X-rays, UV light and agents such as the antitumor
drugs bleomycin and neocarzinostatin or those that generate oxygen radicals.
Apurinic/apyrimidinic (AP) sites form both spontaneously and as highly
cytotoxic intermediates in the removal of the damaged base by the base
excision repair (BER) pathway. DNA repair at the AP sites is initiated by
specific endonuclease cleavage of the phosphodiester backbone. Such
endonucleases are also generally capable of removing blocking groups from the
3'terminus of DNA strand breaks.
AP endonucleases can be classified into two families on the basis of sequence
similarity and structure (cf. family 2 <PDOC00599>). What we call family 1
groups the enzymes listed below [1].
- Escherichia coli exonuclease III (gene xthA) (EC 3.1.11.2).
- Streptococcus pneumoniae and Bacillus subtilis exonuclease A (gene exoA)
(EC=3.1.11.2).
- Mammalian AP endonuclease 1 (AP1) (EC 4.2.99.18).
- Drosophila recombination repair protein 1 (gene Rrp1) (EC=4.2.99.18).
- Arabidopsis thaliana apurinic endonuclease-redox protein (gene arp)
(EC=4.2.99.18).
- Dictyostelium DNA-(apurinic or apyrimidinic site) lyase (gene apeA)
(EC=4.2.99.18).
Except for Rrp1 and arp, these enzymes are proteins of about 300 amino-acid
residues. Rrp1 and arp both contain additional and unrelated sequences in
their N-terminal section (about 400 residues for Rrp1 and 270 for arp).
The structures of bacterial exonuclease III and mammalian AP endonuclease 1
show an alpha/beta-sandwich structure (see <PDB:1HD7; A>) with a fold similar
to that of DNase I (see <PDOC00711>). One or two divalent metal ions such as
magnesium or manganese can bind in the active site [2].
We developed three signature patterns and a profile for this family of
enzymes. The first pattern contains a glutamate which has been shown [3], in
the Escherichia coli enzyme to bind a divalent metal ion such as magnesium or
manganese. The patterns are based on the most conserved regions [4]. We also
developed a profile that spans the entire AP endonucleases family 1 structure.
-Consensus pattern: [APF]-D-[LIVMF](2)-{T}-[LIVM]-Q-E-{G}-K
[E binds a divalent metal ion]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 3.
-Consensus pattern: D-[ST]-[FY]-[RP]-[KHQ]-x(7,8)-[FYWD]-[ST]-[FYW](2)
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Consensus pattern: N-x-G-x-R-[LIVM]-D-[LIVMFYH]-x-[LV]-x-S
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: February 2009 / Text revised; profile added.
[ 1] Barzilay G., Hickson I.D.
"Structure and function of apurinic/apyrimidinic endonucleases."
BioEssays 17:713-719(1995).
PubMed=7661852
[ 2] Beernink P.T., Segelke B.W., Hadi M.Z., Erzberger J.P.,
Wilson D.M. III, Rupp B.
"Two divalent metal ions in the active site of a new crystal form of
human apurinic/apyrimidinic endonuclease, Ape1: implications for the
catalytic mechanism."
J. Mol. Biol. 307:1023-1034(2001).
PubMed=11286553; DOI=10.1006/jmbi.2001.4529
[ 3] Mol C.D., Kuo C.-F., Thayer M.M., Cunningham R.P., Tainer J.A.
"Structure and function of the multifunctional DNA-repair enzyme
exonuclease III."
Nature 374:381-386(1995).
PubMed=7885481; DOI=10.1038/374381a0
[ 4] Kaneda K., Sekiguchi J., Shida T.
"Role of the tryptophan residue in the vicinity of the catalytic
center of exonuclease III family AP endonucleases: AP site recognition
mechanism."
Nucleic Acids Res. 34:1552-1563(2006).
PubMed=16540594; DOI=10.1093/nar/gkl059
{END}
