Protein Family Models

Date:

2024-08-14

Escherichia coli endonuclease III (EC 4.2.99.18) [1] is a DNA repair enzyme that acts both as a DNA N-glycosylase, removing oxidised pyrimidines from DNA, and as an apurinic/apyrimidinic (AP) endonuclease, introducing a single-strand nick at the site from which the damaged base was removed. Endonuclease III is an iron-sulfur protein that binds a single 4Fe-4S cluster. The 4Fe-4S cluster does not seem to be important for catalytic activity, but is probably involved in the proper positioning of the enzyme along the DNA strand [2]. The 4Fe-4S cluster is bound by four cysteines which are all located in a 17 amino acid region at the C-terminal end of endonuclease III. A similar region is also present in the central section of mutY and in the C-terminus of ORF-10 and of the Micro-coccus UV endonuclease [4]. [1]. 7664751. Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure. Thayer MM, Ahern H, Xing D, Cunningham RP, Tainer JA;. EMBO J. 1995;14:4108-4120. [2]. 9045706. Cloning and expression of the cDNA encoding the human homologue of the DNA repair enzyme, Escherichia coli endonuclease III. Hilbert TP, Chaung W, Boorstein RJ, Cunningham RP, Teebor GW;. J Biol Chem. 1997;272:6733-6740. [3]. 16096281. Engineering functional changes in Escherichia coli endonuclease III based on phylogenetic and structural analyses. Watanabe T, Blaisdell JO, Wallace SS, Bond JP;. J Biol Chem. 2005;280:34378-34384. [4]. 16967954. Direct electrochemistry of endonuclease III in the presence and absence of DNA. Gorodetsky AA, Boal AK, Barton JK;. J Am Chem Soc. 2006;128:12082-12083. (from Pfam)

Date:

2024-10-16

The helix-hairpin-helix DNA-binding motif is found to be duplicated in the central domain of RuvA [2]. The HhH domain of DisA, a bacterial checkpoint control protein, is a DNA-binding domain [5]. [1]. 8692686. The helix-hairpin-helix DNA-binding motif: a structural basis for non-sequence-specific recognition of DNA. Doherty AJ, Serpell LC, Ponting CP;. Nucleic Acids Res 1996;24:2488-2497. [2]. 8832889. Crystal structure of DNA recombination protein RuvA and a model for its binding to the Holliday junction. Rafferty JB, Sedelnikova SE, Hargreaves D, Artymiuk PJ, Baker PJ, Sharples GJ, Mahdi AA, Lloyd RG, Rice DW;. Science 1996;274:415-421. [3]. 12832627. An evolutionary analysis of the helix-hairpin-helix superfamily of DNA repair glycosylases. Denver DR, Swenson SL, Lynch M;. Mol Biol Evol 2003;20:1603-1611. [4]. 10908318. Common fold in helix-hairpin-helix proteins. Shao X, Grishin NV;. Nucleic Acids Res 2000;28:2643-2650. [5]. 18439896. Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. Witte G, Hartung S, Buttner K, Hopfner KP;. Mol Cell. 2008;30:167-178. (from Pfam)

Date:

2024-10-16

This family contains a diverse range of structurally related DNA repair proteins. The superfamily is called the HhH-GPD family after its hallmark Helix-hairpin-helix and Gly/Pro rich loop followed by a conserved aspartate [2]. This includes endonuclease III, EC:4.2.99.18 and MutY an A/G-specific adenine glycosylase, both have a C terminal 4Fe-4S cluster. The family also includes 8-oxoguanine DNA glycosylases such as Swiss:P53397. The methyl-CPG binding protein MBD4 Swiss:Q9Z2D7 also contains a related domain [1] that is a thymine DNA glycosylase. The family also includes DNA-3-methyladenine glycosylase II EC:3.2.2.21 and other members of the AlkA family. [1]. 10499592. The thymine glycosylase MBD4 can bind to the product of deamination at methylated CpG sites. Hendrich B, Hardeland U, Ng HH, Jiricny J, Bird A;. Nature 1999;401:301-304. [2]. 10706276. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Bruner SD, Norman DP, Verdine GL;. Nature 2000;403:859-866. (from Pfam)

Date:

2024-10-16

A/G-specific adenine glycosylase prevents DNA mutations by excising adenine (A) from the oxidatively damaged guanine (7,8-dihydro-8-oxoguanine or 7-oxoG):adenine base pair

Date:

2018-04-06

This equivalog HMM identifies mutY members of the PF00730 superfamily (HhH-GPD: Helix-hairpin-helix and Gly/Pro rich loop followed by a conserved aspartate). The major members of the superfamily are nth and mutY.

Gene:

mutY

Date:

2024-05-28

Gene:

mutY

Date:

2021-07-29