{PDOC00599} {PS00729; AP_NUCLEASE_F2_1} {PS00730; AP_NUCLEASE_F2_2} {PS00731; AP_NUCLEASE_F2_3} {PS51432; AP_NUCLEASE_F2_4} {BEGIN} **************************************************** * AP endonucleases family 2 signatures and profile * **************************************************** 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 1 ). What we call family 2 groups the enzymes listed below [1,2]. - Bacterial endonuclease IV (gene nfo) (EC 3.1.21.2). - Fungal and Caenorhabditis elegans apurinic endonuclase APN1 (EC 4.2.99.18). - Dictyostelium endonuclease 4 homolog (EC 3.1.21.2). - Archaeal probable endonuclease 4 homologs (EC 3.1.21.2). - Mimivirus putative endonuclease 4 (EC 3.1.21.2). APN1 and nfo have been shown to be transition metalloproteins that bind three zinc ions [3,4]. The metal-binding sites have been determined from the 3D- structure of Escherichia coli nfo [4,6,7], which shows an alpha/beta-barrel fold (see ) similar to that of other divalent metal-dependent TIM barrel enzymes (see ), such as xylose isomerase (see ). We developed three signature patterns for this family of enzymes. The patterns are based on regions that contain conserved residues involved in zinc-binding. We also developed a profile that covers the entire AP endonuclease family 2 structure. -Consensus pattern: H-[GSAD]-x-Y-[LIF]-[LIMN]-N-[LIVMFCAP]-[AGC] [The H is a zinc ligand] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Consensus pattern: [GSARY]-[LIVMF]-[CT]-[LIVMFY]-D-T-C-H [The D and the H are zinc ligands] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Consensus pattern: [LIVMFW]-H-x-N-[DEG]-[SA]-x(4)-[GNAQ]-x(3)-D-x-H [The 2 H's and the D are zinc ligands] -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] Popoff S.C., Spira A.I., Johnson A.W., Demple B. "Yeast structural gene (APN1) for the major apurinic endonuclease: homology to Escherichia coli endonuclease IV." Proc. Natl. Acad. Sci. U.S.A. 87:4193-4197(1990). PubMed=1693433 [ 2] Barzilay G., Hickson I.D. "Structure and function of apurinic/apyrimidinic endonucleases." BioEssays 17:713-719(1995). PubMed=7661852 [ 3] Levin J.D., Shapiro R., Demple B. "Metalloenzymes in DNA repair. Escherichia coli endonuclease IV and Saccharomyces cerevisiae Apn1." J. Biol. Chem. 266:22893-22898(1991). PubMed=1720775 [ 4] Hosfield D.J., Guan Y., Haas B.J., Cunningham R.P., Tainer J.A. "Structure of the DNA repair enzyme endonuclease IV and its DNA complex: double-nucleotide flipping at abasic sites and three-metal-ion catalysis." Cell 98:397-408(1999). PubMed=10458614 [ 5] Ishchenko A.A., Sanz G., Privezentzev C.V., Maksimenko A.V., Saparbaev M. "Characterisation of new substrate specificities of Escherichia coli and Saccharomyces cerevisiae AP endonucleases." Nucleic Acids Res. 31:6344-6353(2003). PubMed=14576322 [ 6] Ivanov I., Tainer J.A., McCammon J.A. "Unraveling the three-metal-ion catalytic mechanism of the DNA repair enzyme endonuclease IV." Proc. Natl. Acad. Sci. U.S.A. 104:1465-1470(2007). PubMed=17242363; DOI=10.1073/pnas.0603468104 [ 7] Garcin E.D., Hosfield D.J., Desai S.A., Haas B.J., Bjoras M., Cunningham R.P., Tainer J.A. "DNA apurinic-apyrimidinic site binding and excision by endonuclease IV." Nat. Struct. Mol. Biol. 15:515-522(2008). PubMed=18408731; DOI=10.1038/nsmb.1414 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}