{PDOC00956}
{PS01242; ZF_FPG_1}
{PS51066; ZF_FPG_2}
{PS51068; FPG_CAT}
{BEGIN}
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* Formamidopyrimidine-DNA glycosylase signature and profiles *
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Most  damage  to  bases in DNA is repaired by the base excision repair pathway
[1].  The  repair  is  initiated  by  DNA glycosylases, enzymes that recognize
specific   lesion  bases  in  DNA  and  remove  them.  Formamidopyrimidine-DNA
glycosylase  (EC  3.2.2.23) (gene fpg) [2] is a bacterial DNA glycosylase that
recognizes  and  removes damaged bases with a preference for oxidized purines,
such  as  7,8-dihydro-8-oxoguanine  (8-oxoG). Excision of the oxidized guanine
occurs  via  nucleophilic  substitution at C1' by the N-terminal proline . The
aminal   intermediate  thus  formed  rearranges  to  the  Schiff  base,  which
subsequently  undergoes  beta-  and  delta-elimination,  resulting in complete
removal  of  the  lesion  nucleoside  from  DNA.  FPG  has thus also a nicking
activity  that  cleaves  both  the  3'-  and  5'-phosphodiester  bonds  at the
apurinic/apyrimidinic  (AP)  site, leaving a gap in the DNA that has phosphate
groups on both the 5'- and 3'-ends [3].

The  protein  contains  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>)  [4].  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. Residues that
contact  DNA  are  located  in the catalytic domain and in a beta-hairpin loop
formed by the zinc finger [5].

Endonuclease  VIII  (EC  3.2.-.-) (gene nei) is a DNA N-glycosylase with an AP
lyase  activity. It is evolutionary related to FPG. Orthologs of FPG have also
been discovered in mammals (NEIL1, 2 AND 3). NEILs are also active in excising
a  variety  of  oxidatively  damaged bases but show significant differences in
substrate preference [6].

We have developed a signature pattern that covers the four conserved cysteines
of  the  zinc  finger, and, two profiles that span the entire catalytic domain
and zinc finger.

-Consensus pattern: C-x(1,4)-C-[GSANHK]-x(1,2)-[IVML]-x(7,11)-R-
                    [GSANPVLMT]-x(2)-[FYWIL]-C-x(2)-C-Q
-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 first profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the second profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: NEIL1 proteins don't have the zinc finger motif.

-Last update: April 2006 / Pattern revised.

[ 1] Fromme J.C., Verdine G.L.
     "Base excision repair."
     Adv. Protein Chem. 69:1-41(2004).
     PubMed=15588838; DOI=10.1016/S0065-3233(04)69001-2
[ 2] Duwat P., de Oliveira R., Ehrlich S.D., Boiteux S.
     "Repair of oxidative DNA damage in gram-positive bacteria: the
     Lactococcus lactis Fpg protein."
     Microbiology 141:411-417(1995).
     PubMed=7704272
[ 3] Fromme J.C., Banerjee A., Verdine G.L.
     "DNA glycosylase recognition and catalysis."
     Curr. Opin. Struct. Biol. 14:43-49(2004).
     PubMed=15102448; DOI=10.1016/j.sbi.2004.01.003
[ 4] Gilboa R., Zharkov D.O., Golan G., Fernandes A.S., Gerchman S.E.,
     Matz E., Kycia J.H., Grollman A.P., Shoham G.
     "Structure of formamidopyrimidine-DNA glycosylase covalently complexed
     to DNA."
     J. Biol. Chem. 277:19811-19816(2002).
     PubMed=11912217; DOI=10.1074/jbc.M202058200
[ 5] Fromme J.C., Verdine G.L.
     "Structural insights into lesion recognition and repair by the
     bacterial 8-oxoguanine DNA glycosylase MutM."
     Nat. Struct. Biol. 9:544-552(2002).
     PubMed=12055620; DOI=10.1038/nsb809
[ 6] Bandaru V., Sunkara S., Wallace S.S., Bond J.P.
     "A novel human DNA glycosylase that removes oxidative DNA damage and
     is homologous to Escherichia coli endonuclease VIII."
     DNA Repair 1:517-529(2002).
     PubMed=12509226

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