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Distribution and prediction of catalytic domains in 2-oxoglutarate dependent dioxygenases.

Kundu S - BMC Res Notes (2012)

Bottom Line: Access to this repository is by a web server that compares user defined unknown sequences to these pre-defined profiles and outputs a list of predicted catalytic domains.This work, will aid efforts by investigators to screen and characterize putative 2-OG dependent sequences.The profile database will be updated at regular intervals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Army College of Medical Sciences, Delhi Cantt., New Delhi 110010, India. siddharthakundu@theacms.in

ABSTRACT

Background: The 2-oxoglutarate dependent superfamily is a diverse group of non-haem dioxygenases, and is present in prokaryotes, eukaryotes, and archaea. The enzymes differ in substrate preference and reaction chemistry, a factor that precludes their classification by homology studies and electronic annotation schemes alone. In this work, I propose and explore the rationale of using substrates to classify structurally similar alpha-ketoglutarate dependent enzymes.

Findings: Differential catalysis in phylogenetic clades of 2-OG dependent enzymes, is determined by the interactions of a subset of active-site amino acids. Identifying these with existing computational methods is challenging and not feasible for all proteins. A clustering protocol based on validated mechanisms of catalysis of known molecules, in tandem with group specific hidden markov model profiles is able to differentiate and sequester these enzymes. Access to this repository is by a web server that compares user defined unknown sequences to these pre-defined profiles and outputs a list of predicted catalytic domains. The server is free and is accessible at the following URL (http://comp-biol.theacms.in/H2OGpred.html).

Conclusions: The proposed stratification is a novel attempt at classifying and predicting 2-oxoglutarate dependent function. In addition, the server will provide researchers with a tool to compare their data to a comprehensive list of HMM profiles of catalytic domains. This work, will aid efforts by investigators to screen and characterize putative 2-OG dependent sequences. The profile database will be updated at regular intervals.

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Alignment and active site analysis of structurally similar pairs of proteins. Inter-molecular substrate modifying residues (1 or more atoms within 5 A0 of atom(s) of compound of interest) have been tabulated and compared. Color scheme for highlighting: Red – identity, Blue- protein specific, Black – amino acids with their side chains pointing away from the substrate, suggesting a structural role.
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Figure 2: Alignment and active site analysis of structurally similar pairs of proteins. Inter-molecular substrate modifying residues (1 or more atoms within 5 A0 of atom(s) of compound of interest) have been tabulated and compared. Color scheme for highlighting: Red – identity, Blue- protein specific, Black – amino acids with their side chains pointing away from the substrate, suggesting a structural role.

Mentions: This study highlights and discusses the following characteristics of the 2-OG dependent superfamily. There are observable differences in the reaction mechanisms and/or substrates transformed in structurally related enzymes (Table 1, Figure 2). These variations are with reference to the amino acids that border the substrate binding pocket, interact with 2-OG, Fe(II), and participate in alpha-KG specific domain formation. A detailed analysis of predicted domains in previously collated sequences (S0, Additional file2: Table S2), using publically accessible tools, revealed that, the TauD family (PF02668, sequences = 4205, non-redundant PDB ids = 8), consists of enzymes such as: taurine dioxygenase, alkylsulfataseK, asparagine oxygenase, carbapenem synthase C, L-arginine-beta-hydroxylase, and gamma-butyrobetaine hydroxylase among others. Similarly, the PhyH family (PF05721, sequences = 2319, non-redundant PDB ids = 3) encompasses activities of phytanoyl-CoA-dioxygenase, ectoine hydroxylase, and pentalenolactone synthase. Interestingly, all the above catalyze different substrates, clearly demonstrating the lack of discriminatory indices in current literature to delineate function in similar proteins.


Distribution and prediction of catalytic domains in 2-oxoglutarate dependent dioxygenases.

Kundu S - BMC Res Notes (2012)

Alignment and active site analysis of structurally similar pairs of proteins. Inter-molecular substrate modifying residues (1 or more atoms within 5 A0 of atom(s) of compound of interest) have been tabulated and compared. Color scheme for highlighting: Red – identity, Blue- protein specific, Black – amino acids with their side chains pointing away from the substrate, suggesting a structural role.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475032&req=5

Figure 2: Alignment and active site analysis of structurally similar pairs of proteins. Inter-molecular substrate modifying residues (1 or more atoms within 5 A0 of atom(s) of compound of interest) have been tabulated and compared. Color scheme for highlighting: Red – identity, Blue- protein specific, Black – amino acids with their side chains pointing away from the substrate, suggesting a structural role.
Mentions: This study highlights and discusses the following characteristics of the 2-OG dependent superfamily. There are observable differences in the reaction mechanisms and/or substrates transformed in structurally related enzymes (Table 1, Figure 2). These variations are with reference to the amino acids that border the substrate binding pocket, interact with 2-OG, Fe(II), and participate in alpha-KG specific domain formation. A detailed analysis of predicted domains in previously collated sequences (S0, Additional file2: Table S2), using publically accessible tools, revealed that, the TauD family (PF02668, sequences = 4205, non-redundant PDB ids = 8), consists of enzymes such as: taurine dioxygenase, alkylsulfataseK, asparagine oxygenase, carbapenem synthase C, L-arginine-beta-hydroxylase, and gamma-butyrobetaine hydroxylase among others. Similarly, the PhyH family (PF05721, sequences = 2319, non-redundant PDB ids = 3) encompasses activities of phytanoyl-CoA-dioxygenase, ectoine hydroxylase, and pentalenolactone synthase. Interestingly, all the above catalyze different substrates, clearly demonstrating the lack of discriminatory indices in current literature to delineate function in similar proteins.

Bottom Line: Access to this repository is by a web server that compares user defined unknown sequences to these pre-defined profiles and outputs a list of predicted catalytic domains.This work, will aid efforts by investigators to screen and characterize putative 2-OG dependent sequences.The profile database will be updated at regular intervals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Army College of Medical Sciences, Delhi Cantt., New Delhi 110010, India. siddharthakundu@theacms.in

ABSTRACT

Background: The 2-oxoglutarate dependent superfamily is a diverse group of non-haem dioxygenases, and is present in prokaryotes, eukaryotes, and archaea. The enzymes differ in substrate preference and reaction chemistry, a factor that precludes their classification by homology studies and electronic annotation schemes alone. In this work, I propose and explore the rationale of using substrates to classify structurally similar alpha-ketoglutarate dependent enzymes.

Findings: Differential catalysis in phylogenetic clades of 2-OG dependent enzymes, is determined by the interactions of a subset of active-site amino acids. Identifying these with existing computational methods is challenging and not feasible for all proteins. A clustering protocol based on validated mechanisms of catalysis of known molecules, in tandem with group specific hidden markov model profiles is able to differentiate and sequester these enzymes. Access to this repository is by a web server that compares user defined unknown sequences to these pre-defined profiles and outputs a list of predicted catalytic domains. The server is free and is accessible at the following URL (http://comp-biol.theacms.in/H2OGpred.html).

Conclusions: The proposed stratification is a novel attempt at classifying and predicting 2-oxoglutarate dependent function. In addition, the server will provide researchers with a tool to compare their data to a comprehensive list of HMM profiles of catalytic domains. This work, will aid efforts by investigators to screen and characterize putative 2-OG dependent sequences. The profile database will be updated at regular intervals.

Show MeSH