Microbial inositol polyphosphate metabolic pathway as drug development target
| Autor: | Paloma Portela-Torres, Adolfo Saiardi, Miranda S. C. Wilson, Yann Desfougères, Cristina Azevedo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Antifungal Agents Inositol Phosphates Trypanosoma brucei brucei 03 medical and health sciences chemistry.chemical_compound Drug Development Genetics Animals Humans Inositol Inositol phosphate Molecular Biology chemistry.chemical_classification 030102 biochemistry & molecular biology biology Kinase Polyphosphate Cryptococcosis biology.organism_classification Trypanocidal Agents Metabolic pathway Trypanosomiasis African 030104 developmental biology Enzyme chemistry Biochemistry Cryptococcus neoformans Molecular Medicine Phosphorylation Eukaryote |
| Zdroj: | Advances in Biological Regulation. 67:74-83 |
| ISSN: | 2212-4926 |
| DOI: | 10.1016/j.jbior.2017.09.007 |
| Popis: | Inositol polyphosphates are a diverse and multifaceted class of intracellular messengers omnipresent in eukaryotic cells. These water-soluble molecules regulate many aspects of fundamental cell physiology. Removing this metabolic pathway is deleterious: inositol phosphate kinase null mutations can result in lethality or substantial growth phenotypes. Inositol polyphosphate synthesis occurs through the actions of a set of kinases that phosphorylate phospholipase-generated IP3 to higher phosphorylated forms, such as the fully phosphorylated IP6 and the inositol pyrophosphates IP7 and IP8. Unicellular organisms have a reduced array of the kinases for synthesis of higher phosphorylated inositol polyphosphates, while human cells possess two metabolic routes to IP6. The enzymes responsible for inositol polyphosphate synthesis have been identified in all eukaryote genomes, although their amino acid sequence homology is often barely detectable by common search algorithms. Homology between human and microbial inositol phosphate kinases is restricted to a few catalytically important residues. Recent studies of the inositol phosphate metabolic pathways in pathogenic fungi (Cryptococcus neoformans) and protozoa (Trypanosome brucei) have revealed the importance of the highly phosphorylated inositol polyphosphates to the fitness and thus virulence of these pathogens. Given this, identification of inositol kinase inhibitors specifically targeting the kinases of pathogenic microorganisms is desirable and achievable. |
| Databáze: | OpenAIRE |
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