Abstract
Could a disjoint group of enzymes synchronize their activities and execute a complex multi-step, measurable, and reproducible response? Here, I surmise that the alpha-ketoglutarate dependent superfamily of non-haem iron (II) dioxygenases could influence cell physiology as a cohesive unit, and that the broad spectra of substrates transformed is an absolute necessity to this portrayal. This eclectic group comprises members from all major taxa, and participates in pesticide breakdown, hypoxia signaling, and osmotic stress neutralization. The oxidative decarboxylation of 2-oxoglutarate to succinate is coupled with a concomitant substrate hydroxylation and, in most cases, is followed by an additional specialized conversion. The domain profile of a protein sequence was used as an index of miscellaneous reaction chemistry and interpreted alongside existent kinetic data in a linear model of integrated function. Statistical parameters were inferred by the creation of a novel, empirically motivated flat-file database of over 3800 sequences (DB2OG) with putative 2-oxoglutarate dependent activity. The collated information was categorized on the basis of existing annotation schema. The data suggests that 2OG-dependent enzymes incorporate several desirable features of a systems level player. DB2OG, is free, accessible without a login to all users, and available at the following URL (http://comp-biol.theacms.in/DB2OG.html).
Highlights
Physiology is an unmeasured outcome of a complex undefined molding of several underlying, disparate, and interdependent molecular level events
Given the inherent complexity of biological systems and the varied approximations of existent models, a cumulative error term that summarizes inestimable and excluded data points is an obligatory element of any representation under consideration
This may be minimized by usage of the logical OR/AND functions to filter the profiles (Figure 1)
Summary
Physiology is an unmeasured outcome of a complex undefined molding of several underlying, disparate, and interdependent molecular level events. A novel database, DB2OG, was constructed wherein predicted catalytic domains of biochemically validated enzymes were mapped onto a set of sequences which had no supporting laboratory data.
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