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2018-03-05

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cc by (c) Cova et al., 2018
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/121294

The Apicomplexa-specific glucosamine-6-phosphate N-acetyltransferase gene family encodes a key enzyme for glycoconjugate synthesis with potential as therapeutic target

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http://dx.doi.org/10.1038/s41598-018-22441-3

Resum

Apicomplexa form a phylum of obligate parasitic protozoa of great clinical and veterinary importance. These parasites synthesize glycoconjugates for their survival and infectivity, but the enzymatic steps required to generate the glycosylation precursors are not completely characterized. In particular, glucosamine-phosphate N-acetyltransferase (GNA1) activity, needed to produce the essential UDP-N-acetylglucosamine (UDP-GlcNAc) donor, has not been identified in any Apicomplexa. We scanned the genomes of Plasmodium falciparum and representatives from six additional main lineages of the phylum for proteins containing the Gcn5-related N-acetyltransferase (GNAT) domain. One family of GNAT-domain containing proteins, composed by a P. falciparum sequence and its six apicomplexan orthologs, rescued the growth of a yeast temperature-sensitive GNA1 mutant. Heterologous expression and in vitro assays confirmed the GNA1 enzymatic activity in all lineages. Sequence, phylogenetic and synteny analyses suggest an independent origin of the Apicomplexa-specific GNA1 family, parallel to the evolution of a different GNA1 family in other eukaryotes. The inability to disrupt an otherwise modifiable gene target suggests that the enzyme is essential for P. falciparum growth. The relevance of UDP-GlcNAc for parasite viability, together with the independent evolution and unique sequence features of Apicomplexa GNA1, highlights the potential of this enzyme as a selective therapeutic target against apicomplexans.

Matèries

Glicòmica, Malalties parasitàries

Matèries (anglès)

Glycomics, Parasitic diseases

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Articles publicats en revistes (ISGlobal)
<b>Publicacions de projectes de recerca finançats per la UE</b>

Citació

COVA, Marta, LÓPEZ GUTIÉRREZ, Borja, ARTIGAS JERÓNIMO, Sara, GONZÁLEZ DÍAZ, Aida, BANDINI, Giulia, MAERE, Steven, CARRETERO PAULET, Lorenzo, IZQUIERDO LÁZARO, Luis. The Apicomplexa-specific glucosamine-6-phosphate
                N-acetyltransferase gene family encodes a key enzyme for
                glycoconjugate synthesis with potential as therapeutic target. _Scientific Reports_. 2018. Vol. 8, núm. 4005. [consulta: 26 de febrer de 2026]. ISSN: 2045-2322. [Disponible a: https://hdl.handle.net/2445/121294]

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