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Unity in diversity, a systems approach to regulating plant cell physiology by 2-oxoglutarate-dependent dioxygenases.

Kundu S - Front Plant Sci (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Computational and Integrative Sciences, Jawaharlal Nehru University New Delhi, India.

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).

No MeSH data available.


Related in: MedlinePlus

2-oxoglutarate-dependent dioxygenases as stimulus reinforcers. (A) Anabolic (GA20ox, GA3ox) and catabolic (GA2ox) alpha-ketoglutarate dependent enzymes function to prepare a cell mileau conducive to growth and development (increased formation and storage of alkaloids, expansins, glycosylases, and decreased formation of lignins) and a modulatory antioxidant process (formation of flavonoids). (B) Plant P4Hs catalyze the hydroxylation of proline-rich peptide segments of cell wall glycoproteins, stabilizing the macromolecule. Conversely, decreased activity might result in loosely networked unstable components, that are required for continued growth.
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Figure 7: 2-oxoglutarate-dependent dioxygenases as stimulus reinforcers. (A) Anabolic (GA20ox, GA3ox) and catabolic (GA2ox) alpha-ketoglutarate dependent enzymes function to prepare a cell mileau conducive to growth and development (increased formation and storage of alkaloids, expansins, glycosylases, and decreased formation of lignins) and a modulatory antioxidant process (formation of flavonoids). (B) Plant P4Hs catalyze the hydroxylation of proline-rich peptide segments of cell wall glycoproteins, stabilizing the macromolecule. Conversely, decreased activity might result in loosely networked unstable components, that are required for continued growth.

Mentions: Four kinds of bias may be identified in 2OG-dependent plant dioxygenases (Figures 4, 5): (a) competing routes of reactions with shared substrate preferences. In the event of a flux toward a particular pathway, metabolites of the other decline reciprocally. The major biosynthetic channel of the flavonoids (Figure 6B), is the routing of p-coumaroyl-CoA through chalcone synthase (CHS, EC 2.3.1.74), in competition with the monolignol synthesizing hydroxycinnamoyl-CoA: shikimate/quinate hydroxycinnamoyl-CoA transferase (HCT, EC 2.3.1.133) (Burbulis et al., 1996; Hoffmann et al., 2004; Figure 6), (b) continued product utilization is an alternate strategy to favor certain reactions, thereby, introducing a dominant direction (L3a ⇋ L4a; Figure 4B). Activated L-methionine (S-adenosylmethionine, SAM) is the precursor for both ACC and nicotianamine (NA), which in the presence of Fe-deficiency, leads to the unhindered synthesis and efflux of the mugineic acids (MAs) which function as phytosiderophores (Nakanishi et al., 2000; Nozoye et al., 2011; Figure 6), (c) co-factor driven altered enzymatic activity of gibberellic acid (GA) metabolizing enzymes (GA −20, −3, −2 oxidases; EC 1.14.11.x, x = −, 15, 13) (Figure 7A). The kinetics (GA3O, KmFe ≅ 0.2 mM; GA2O, KmFe ≅ 1.0 mM) (Smith and MacMillan, 1984; Kwak et al., 1988), suggest that if cytosolic iron levels drop to levels below 1mM, the activity of the catabolic GA2ox approximates a value. This balance between the highly active GA −1, −3, −4, −5, and −7 and the inactive GAs −8, −34, −97, −110 (Hedden and Phillips, 2000a,b) is critical to seed dormancy, root and shoot development, flowering, and generalized cell elongation. GAs serve as master regulators of other enzyme systems as well, and (d) initiate a cascade of reactions utilizing high affinity AKG-dependent enzymes for small molecule modifiers. Activated molecular dioxygen is a key component of these enzymes and could diffuse out if catalysis was compromised. The active site geometry of ACCO (KmFe ≅ 0.059 mM; Nagahama et al., 1991) not just permits FETs, but may mitigate the effects of co-substrate withdrawal as well. The free radicals generated subsequently by O2 (ROS and RNS) amplify the response manifold. The rapid generation and involvement of substrate radicals (lipid peroxidation of polyenes), could translate into an equally swift consumption of potential substrates, which indirectly, could introduce the requisite bias.


Unity in diversity, a systems approach to regulating plant cell physiology by 2-oxoglutarate-dependent dioxygenases.

Kundu S - Front Plant Sci (2015)

2-oxoglutarate-dependent dioxygenases as stimulus reinforcers. (A) Anabolic (GA20ox, GA3ox) and catabolic (GA2ox) alpha-ketoglutarate dependent enzymes function to prepare a cell mileau conducive to growth and development (increased formation and storage of alkaloids, expansins, glycosylases, and decreased formation of lignins) and a modulatory antioxidant process (formation of flavonoids). (B) Plant P4Hs catalyze the hydroxylation of proline-rich peptide segments of cell wall glycoproteins, stabilizing the macromolecule. Conversely, decreased activity might result in loosely networked unstable components, that are required for continued growth.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356072&req=5

Figure 7: 2-oxoglutarate-dependent dioxygenases as stimulus reinforcers. (A) Anabolic (GA20ox, GA3ox) and catabolic (GA2ox) alpha-ketoglutarate dependent enzymes function to prepare a cell mileau conducive to growth and development (increased formation and storage of alkaloids, expansins, glycosylases, and decreased formation of lignins) and a modulatory antioxidant process (formation of flavonoids). (B) Plant P4Hs catalyze the hydroxylation of proline-rich peptide segments of cell wall glycoproteins, stabilizing the macromolecule. Conversely, decreased activity might result in loosely networked unstable components, that are required for continued growth.
Mentions: Four kinds of bias may be identified in 2OG-dependent plant dioxygenases (Figures 4, 5): (a) competing routes of reactions with shared substrate preferences. In the event of a flux toward a particular pathway, metabolites of the other decline reciprocally. The major biosynthetic channel of the flavonoids (Figure 6B), is the routing of p-coumaroyl-CoA through chalcone synthase (CHS, EC 2.3.1.74), in competition with the monolignol synthesizing hydroxycinnamoyl-CoA: shikimate/quinate hydroxycinnamoyl-CoA transferase (HCT, EC 2.3.1.133) (Burbulis et al., 1996; Hoffmann et al., 2004; Figure 6), (b) continued product utilization is an alternate strategy to favor certain reactions, thereby, introducing a dominant direction (L3a ⇋ L4a; Figure 4B). Activated L-methionine (S-adenosylmethionine, SAM) is the precursor for both ACC and nicotianamine (NA), which in the presence of Fe-deficiency, leads to the unhindered synthesis and efflux of the mugineic acids (MAs) which function as phytosiderophores (Nakanishi et al., 2000; Nozoye et al., 2011; Figure 6), (c) co-factor driven altered enzymatic activity of gibberellic acid (GA) metabolizing enzymes (GA −20, −3, −2 oxidases; EC 1.14.11.x, x = −, 15, 13) (Figure 7A). The kinetics (GA3O, KmFe ≅ 0.2 mM; GA2O, KmFe ≅ 1.0 mM) (Smith and MacMillan, 1984; Kwak et al., 1988), suggest that if cytosolic iron levels drop to levels below 1mM, the activity of the catabolic GA2ox approximates a value. This balance between the highly active GA −1, −3, −4, −5, and −7 and the inactive GAs −8, −34, −97, −110 (Hedden and Phillips, 2000a,b) is critical to seed dormancy, root and shoot development, flowering, and generalized cell elongation. GAs serve as master regulators of other enzyme systems as well, and (d) initiate a cascade of reactions utilizing high affinity AKG-dependent enzymes for small molecule modifiers. Activated molecular dioxygen is a key component of these enzymes and could diffuse out if catalysis was compromised. The active site geometry of ACCO (KmFe ≅ 0.059 mM; Nagahama et al., 1991) not just permits FETs, but may mitigate the effects of co-substrate withdrawal as well. The free radicals generated subsequently by O2 (ROS and RNS) amplify the response manifold. The rapid generation and involvement of substrate radicals (lipid peroxidation of polyenes), could translate into an equally swift consumption of potential substrates, which indirectly, could introduce the requisite bias.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Computational and Integrative Sciences, Jawaharlal Nehru University New Delhi, India.

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).

No MeSH data available.


Related in: MedlinePlus