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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/190615
Plasmodium falciparum Apicomplexan-Specific Glucosamine-6-Phosphate <i>N</i>-Acetyltransferase Is Key for Amino Sugar Metabolism and Asexual Blood Stage Development.
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--- - i: - N - N - O - N - Plasmodium falciparum -
Cryptosporidium parvum - P. falciparum - N - N - P. falciparum -
C. parvum b: - IMPORTANCE content: - UDP- - "-acetylglucosamine
(UDP-GlcNAc), the main product of the hexosamine biosynthetic
pathway, is an important metabolite in protozoan parasites since
its sugar moiety is incorporated into
glycosylphosphatidylinositol (GPI) glycolipids and " - "- and "
- "-linked glycans. Apicomplexan parasites have a hexosamine
pathway comparable to other eukaryotic organisms, with the
exception of the glucosamine-phosphate " - "-acetyltransferase
(GNA1) enzymatic step that has an independent evolutionary
origin and significant differences from nonapicomplexan GNA1s.
By using conditional genetic engineering, we demonstrate the
requirement of GNA1 for the generation of a pool of UDP-GlcNAc
and for the development of intraerythrocytic asexual " - "
parasites. Furthermore, we present the 1.95\xE2\x80\x89\xC3\x85
resolution structure of the GNA1 ortholog from " - ", an
apicomplexan parasite which is a leading cause of diarrhea in
developing countries, as a surrogate for " - " GNA1. The
in-depth analysis of the crystal shows the presence of specific
residues relevant for GNA1 enzymatic activity that are further
investigated by the creation of site-specific mutants. The
experiments reveal distinct features in apicomplexan GNA1
enzymes that could be exploitable for the generation of
selective inhibitors against these parasites, by targeting the
hexosamine pathway. This work underscores the potential of
apicomplexan GNA1 as a drug target against malaria." - "
Apicomplexan parasites cause a major burden on global health and
economy. The absence of treatments, the emergence of resistances
against available therapies, and the parasite's ability to
manipulate host cells and evade immune systems highlight the
urgent need to characterize new drug targets to treat infections
caused by these parasites. We demonstrate that
glucosamine-6-phosphate " - -acetyltransferase (GNA1), required
for the biosynthesis of UDP- - "-acetylglucosamine (UDP-GlcNAc),
is essential for " - " asexual blood stage development and that
the disruption of the gene encoding this enzyme quickly causes
the death of the parasite within a life cycle. The
high-resolution crystal structure of the GNA1 ortholog from the
apicomplexan parasite " - ", used here as a surrogate,
highlights significant differences from human GNA1. These
divergences can be exploited for the design of specific
inhibitors against the malaria parasite."
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CHI, Jordi, COVA, Marta, RIVAS, Matilde de las, MEDINA, Ana, BORGES, Rafael junqueir, LEIVAR, Pablo, PLANAS I ANZANO, Antoni, USÓN FINKENZELLER, Isabel, HURTADO GUERRERO, Ramón, IZQUIERDO, Luis. Plasmodium falciparum Apicomplexan-Specific
Glucosamine-6-Phosphate <i>N</i>-Acetyltransferase
Is Key for Amino Sugar Metabolism and Asexual Blood Stage
Development.. _mBio _. 2020. Vol. 11, núm. 5. [consulta: 8 de gener de 2026]. ISSN: 2150-7511. [Disponible a: https://hdl.handle.net/2445/190615]