Experimental characterization of two archaeal inosine 5'-monophosphate cyclohydrolases

Hunter, Caroline A.; Plymale, Nicholas I.; Smee, Kevin M.; Sarisky, Catherine A.

doi:10.1371/journal.pone.0223983

Cited by 2 publications

(1 citation statement)

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“…One of these IMP cyclohydrolases is of the type identified in early eukaryotic studies, and the other is an unrelated protein with the same function (archaeal‐IMP c , EC 3.5.4.10) (Figure 1). 47,48 Each are equally common in the species we have investigated (Figure 2).…”

Section: Archaea and An Alternative Purine Lifestylementioning

confidence: 99%

Surveying purine biosynthesis across the domains of life unveils promising drug targets in pathogens

Chua

Fraser

2020

Immunol Cell Biol

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Purines play an integral role in cellular processes such as energy metabolism, cell signaling and encoding the genetic makeup of all living organisms—ensuring that the purine metabolic pathway is maintained across all domains of life. To gain a deeper understanding of purine biosynthesis via the de novo biosynthetic pathway, the genes encoding purine metabolic enzymes from 35 archaean, 69 bacterial and 99 eukaryotic species were investigated. While the classic elements of the canonical purine metabolic pathway were utilized in all domains, a subset of familiar biochemical roles was found to be performed by unrelated proteins in some members of the Archaea and Bacteria. In the Bacteria, a major differentiating feature of de novo purine biosynthesis is the increasing prevalence of gene fusions, where two or more purine biosynthesis enzymes that perform consecutive biochemical functions in the pathway are encoded by a single gene. All species in the Eukaryota exhibited the most common fusions seen in the Bacteria, in addition to new gene fusions to potentially increase metabolic flux. This complexity is taken further in humans, where a reversible biomolecular assembly of enzymes known as the purinosome has been identified, allowing short‐term regulation in response to metabolic cues while expanding on the benefits that can come from gene fusion. By surveying purine metabolism across all domains of life, we have identified important features of the purine biosynthetic pathway that can potentially be exploited as prospective drug targets.

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Section: Archaea and An Alternative Purine Lifestylementioning

confidence: 99%