Abstract
Structure-guided analysis of the new dimeric dUTPase family revealed its sequence relationship to the phage T4 dCTPase, phosphoribosyl-ATP pyrophosphatase HisE, NTP pyrophosphatase MazG, and several uncharacterized protein families, including the human protein XTP3TPA (RS21-C6), which is overexpressed in embryonic and cancer cells. Comparison with the recently determined structure of a MazG-like protein from Sulfolobus solfataricus supported the unification of these enzymes in one superfamily of all-alpha NTP pyrophosphatases, suggesting that dimeric dUTPases evolved from a tetrameric MazG-like ancestor by gene duplication. Analysis of the structure of the Sulfolobus MazG points to 2-hydroxyadenosine (isoguanosine) triphosphate, a product of oxidative damage of ATP, as the most likely substrate. We predict that uncharacterized members of this superfamily perform "house-cleaning" functions by hydrolyzing abnormal NTPs and are functionally analogous to the structurally unrelated hydrolases of the Nudix superfamily. We outline probable tertiary and quaternary structures of the all-alpha NTP pyrophosphatase superfamily members. (c) 2005 Elsevier Ltd. All rights reserved.
| Original language | English |
|---|---|
| Pages (from-to) | 243-255 |
| Number of pages | 13 |
| Journal | Journal of Molecular Biology |
| Volume | 347 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 25 Mar 2005 |
Keywords
- histidine biosynthesis
- non-canonical nucleotides
- mutagenesis
- gene silencing
- oxidative damage
- PROTEIN SECONDARY STRUCTURE
- NUCLEOSIDE TRIPHOSPHATE PYROPHOSPHOHYDROLASE
- GENE-EXPRESSION
- ESCHERICHIA-COLI
- STRUCTURE PREDICTION
- CRYSTAL-STRUCTURE
- LEISHMANIA-MAJOR
- TRYPANOSOMA-CRUZI
- NUDIX HYDROLASES
- DNA METHYLATION