Subsystem: dNTP triphosphohydrolase protein family
This subsystem's description is:
This SS encodes the dNTP triphosphohydrolase family, as well as various gene families (labeled AUX) that tend to cluster on the chromosome with members of it's different subgroups
The founding member of this family was originally isolated from E. coli and shown to hydrolyze dGTP to deoxyguanosine and tripolyphosphate (Seto et al., 1998). Homologous triphosphohydrolase in Thermus thermophilus HB8 was determined to hydrolyze all canonical dNTPs through a complex activation mechanism (Kondo et al., 2004). Recently 2 additional members of this family were characterized in Pseudomonas aeruginosa: PA1124 (has a preference for dGTP, similar to the E. coli enzyme,) and PA3043 (displays broad substrate specificity) (Mega et al., 2009)
Given very few experimentally characterized members, it is impossible to predict accurately substrate specificity of all it's members, widely distributed in eubacteria, Archaea and Eukaryotes. An attempt was made in this SS to disambiguate major subgroups of this family. Annotations of the first 3 subfamilies are based on (Mega et al., 2009, PMID: 19438719) and comprise:
>> Deoxyguanosinetriphosphate triphosphohydrolase (EC 3.1.5.1), subgroup 1 -
- represented by E. coli Dgt (b0160) and P. aeruginosa PA1124, preferentially hydrolyze dGTP without an activator; also contains the homologs of Gammaproteobacteria. EC-Dgt (and likely this entire subfamily) has mutator activity with unusual specificity (Gawel et al., 2008). Based on analysis of these effects, authors concluded, that alterations of the dGTP pools and/or levels of some modified dGTP (or dNTP) derivatives could affect the fidelity of DNA replication and, hence, account for the overall mutator effects (Gawel et al., 2008)
>> dNTP triphosphohydrolase, broad substrate specificity, subgroup 2
- represented by TTHA0412 from Thermus thermophilus HB8, hydrolyzes multiple kinds of dNTP upon activation by binding of an activator (Kondo et al., 2004), contains the homologs of Alphaproteobacteria, Betaproteobacteria and Deinococci. Function of this subfamily is not clear, but its tight clustering on the chromosome with DNA primase might indicate its role in maintaining concentrations of canonical or noncanonical dNTP in the cell.
>> dNTP triphosphohydrolase, broad substrate specificity, subgroup 3
- represented by P. aeruginosa PA3043, hydrolyze multiple kinds of dNTP without an activator; also contains the homologs of Betaproteobacteria, Gammaproteobacteria, Epsilon-bacteria and Bacteroides. It was noted (Mega et al., 2009) that the observed Km values for PA1124 and PA3043 (and hence, possibly for other members of subgroups #2 and #3) are higher than the estimated intracellular concentrations of dNTPs. Therefore, it is possible that these enzymes hydrolyze different substrates in vivo.
Additional subfamilies encoded in this SS were delineated based on analysis of phylogenetic trees. To our knowledge these groups have no experimentally characterized members currently:
>> Putative dNTP triphosphohydrolase, associated with nucleotidase YfbR
>> Putative dNTP triphosphohydrolase, Firmicutes subgroup
>> Putative dNTP triphosphohydrolase, Archaeal subgroup
>> dNTP triphosphohydrolase, putative
References
Seto D, Bhatnagar SK, Bessman MJ (1988). "The purification and properties of deoxyguanosine triphosphate triphosphohydrolase from Escherichia coli." J Biol Chem 1988;263(3);1494-9. PMID: 2826481
Huber HE, Beauchamp BB & Richardson CC (1988) Escherichia coli dGTP triphosphohydrolase is inhibited by gene 1.2 protein of bacteriophage T7. J Biol Chem 263, 1354913556
Mega R, Kondo N, Nakagawa N, Kuramitsu S, Masui R. 2009. Two dNTP triphosphohydrolases from Pseudomonas aeruginosa possess diverse substrate specificities. FEBS J., 276(12):3211-21. PMID: 19438719
Gawel D, Hamilton MD & Schaaper RM (2008) A novel mutator of Escherichia coli carrying a defect in the dgt Gene, encoding a dGTP triphosphohydrolase. J Bacteriol 190, 69316939.
Kondo N, Kuramitsu S & Masui R (2004) Biochemical characterization of TT1383 from Thermus thermophilus identifies a novel dNTP triphosphohydrolase activity stimulated by dATP and dTTP. J Biochem (Tokyo) 136, 221231. PMID: 15496593
Kondo N, Nakagawa N, Ebihara A, Chen L, Liu ZJ, Wang BC, Yokoyama S, Kuramitsu S & Masui R (2007) Structure of dNTP-inducible dNTP triphosphohydrolase: insight into broad specificity for dNTPs and triphosphohydrolase-type hydrolysis. Acta Crystallogr D Biol Crystallogr 63, 230239. PMID: 17242516
For more information, please check out the description and the additional notes tabs, below
| Diagram | Functional Roles | Subsystem Spreadsheet | Description | ||||||||||||||||||||||||||||||||||||||||||||||||||
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This SS encodes the dNTP triphosphohydrolase family, as well as various gene families (labeled AUX) that tend to cluster on the chromosome with members of it's different subgroups The founding member of this family was originally isolated from E. coli and shown to hydrolyze dGTP to deoxyguanosine and tripolyphosphate (Seto et al., 1998). Homologous triphosphohydrolase in Thermus thermophilus HB8 was determined to hydrolyze all canonical dNTPs through a complex activation mechanism (Kondo et al., 2004). Recently 2 additional members of this family were characterized in Pseudomonas aeruginosa: PA1124 (has a preference for dGTP, similar to the E. coli enzyme,) and PA3043 (displays broad substrate specificity) (Mega et al., 2009) Given very few experimentally characterized members, it is impossible to predict accurately substrate specificity of all it's members, widely distributed in eubacteria, Archaea and Eukaryotes. An attempt was made in this SS to disambiguate major subgroups of this family. Annotations of the first 3 subfamilies are based on (Mega et al., 2009, PMID: 19438719) and comprise: >> Deoxyguanosinetriphosphate triphosphohydrolase (EC 3.1.5.1), subgroup 1 - - represented by E. coli Dgt (b0160) and P. aeruginosa PA1124, preferentially hydrolyze dGTP without an activator; also contains the homologs of Gammaproteobacteria. EC-Dgt (and likely this entire subfamily) has mutator activity with unusual specificity (Gawel et al., 2008). Based on analysis of these effects, authors concluded, that alterations of the dGTP pools and/or levels of some modified dGTP (or dNTP) derivatives could affect the fidelity of DNA replication and, hence, account for the overall mutator effects (Gawel et al., 2008) >> dNTP triphosphohydrolase, broad substrate specificity, subgroup 2 - represented by TTHA0412 from Thermus thermophilus HB8, hydrolyzes multiple kinds of dNTP upon activation by binding of an activator (Kondo et al., 2004), contains the homologs of Alphaproteobacteria, Betaproteobacteria and Deinococci. Function of this subfamily is not clear, but its tight clustering on the chromosome with DNA primase might indicate its role in maintaining concentrations of canonical or noncanonical dNTP in the cell. >> dNTP triphosphohydrolase, broad substrate specificity, subgroup 3 - represented by P. aeruginosa PA3043, hydrolyze multiple kinds of dNTP without an activator; also contains the homologs of Betaproteobacteria, Gammaproteobacteria, Epsilon-bacteria and Bacteroides. It was noted (Mega et al., 2009) that the observed Km values for PA1124 and PA3043 (and hence, possibly for other members of subgroups #2 and #3) are higher than the estimated intracellular concentrations of dNTPs. Therefore, it is possible that these enzymes hydrolyze different substrates in vivo. Additional subfamilies encoded in this SS were delineated based on analysis of phylogenetic trees. To our knowledge these groups have no experimentally characterized members currently: >> Putative dNTP triphosphohydrolase, associated with nucleotidase YfbR >> Putative dNTP triphosphohydrolase, Firmicutes subgroup >> Putative dNTP triphosphohydrolase, Archaeal subgroup >> dNTP triphosphohydrolase, putative References Seto D, Bhatnagar SK, Bessman MJ (1988). "The purification and properties of deoxyguanosine triphosphate triphosphohydrolase from Escherichia coli." J Biol Chem 1988;263(3);1494-9. PMID: 2826481 Huber HE, Beauchamp BB & Richardson CC (1988) Escherichia coli dGTP triphosphohydrolase is inhibited by gene 1.2 protein of bacteriophage T7. J Biol Chem 263, 1354913556 Mega R, Kondo N, Nakagawa N, Kuramitsu S, Masui R. 2009. Two dNTP triphosphohydrolases from Pseudomonas aeruginosa possess diverse substrate specificities. FEBS J., 276(12):3211-21. PMID: 19438719 Gawel D, Hamilton MD & Schaaper RM (2008) A novel mutator of Escherichia coli carrying a defect in the dgt Gene, encoding a dGTP triphosphohydrolase. J Bacteriol 190, 69316939. Kondo N, Kuramitsu S & Masui R (2004) Biochemical characterization of TT1383 from Thermus thermophilus identifies a novel dNTP triphosphohydrolase activity stimulated by dATP and dTTP. J Biochem (Tokyo) 136, 221231. PMID: 15496593 Kondo N, Nakagawa N, Ebihara A, Chen L, Liu ZJ, Wang BC, Yokoyama S, Kuramitsu S & Masui R (2007) Structure of dNTP-inducible dNTP triphosphohydrolase: insight into broad specificity for dNTPs and triphosphohydrolase-type hydrolysis. Acta Crystallogr D Biol Crystallogr 63, 230239. PMID: 17242516 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
