Abstract
BackgroundThe 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.FindingsDifferential 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).ConclusionsThe 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.
Highlights
The 2-oxoglutarate dependent superfamily is a diverse group of non-haem dioxygenases, and is present in prokaryotes, eukaryotes, and archaea
The server will provide researchers with a tool to compare their data to a comprehensive list of Hidden Markov model (HMM) profiles of catalytic domains
Analysis of active site residues was done with the SPDBV (Swiss PDB viewer), alignments and cladograms were generated with the STRAP suite of programs (Structural Alignment of Proteins), and HMMER 3.0 was used for model building, analysis, database construction, and similarity studies with user defined input sequences [24-26]
Summary
The 2-oxoglutarate dependent superfamily is a diverse group of non-haem dioxygenases, and is present in prokaryotes, eukaryotes, and archaea. The 2-OG dependent subgroup comprises members that are non-haem in character, require iron (II), and 2oxoglutarate as a co-substrate for catalysis Members of this superfamily are ubiquitous in nature, possess a DSBH fold (Double Stranded Beta-Helical), and the major coordinating amino acids are (HX[DE]XnH). Pfam is a repository of protein families formed by sequence and structural similarity, and organization of distant domain architectures; SMART searches protein sequences for pre-defined regulatory domain architectures using Pfam, signal peptides, trans-membrane helices, regions of low complexity, and internal repeats; SUPERFAMILY and Gene3D integrate fold and domain data with genomic and taxonomic information to provide a comprehensive resource for proteins of interest [16-20] These algorithms, despite providing initial pointers to the reaction chemistry of novel
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