# name
Plasmodium falciparum Apicomplexan-Specific
Glucosamine-6-Phosphate N-Acetyltransferase
Is Key for Amino Sugar Metabolism and Asexual Blood Stage
Development.

# metadata.dc.description.abstract[].value
--- - 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."

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Plasmodium falciparum Apicomplexan-Specific
Glucosamine-6-Phosphate N-Acetyltransferase
Is Key for Amino Sugar Metabolism and Asexual Blood Stage
Development.