biostudies-literatureFrasse PMNational Institute of Allergy and Infectious DiseasesNSERCNICHD NIH HHSNIAID NIH HHSBurroughs Wellcome FundNational Institutes of HealthCIHR ICRCanadian Institutes of Health ResearchCIHR101550https://www.ebi.ac.uk/biostudies/studies/S-EPMC8808168biostudies-literatureUnknown298(2)The malaria-causing parasite Plasmodium falciparum is responsible for over 200 million infections and 400,000 deaths per year. At multiple stages during its complex life cycle, P. falciparum expresses several essential proteins tethered to its surface by glycosylphosphatidylinositol (GPI) anchors, which are critical for biological processes such as parasite egress and reinvasion of host red blood cells. Targeting this pathway therapeutically has the potential to broadly impact parasite development across several life stages. Here, we characterize an upstream component of parasite GPI anchor biosynthesis, the putative phosphomannomutase (PMM) (EC 5.4.2.8), HAD5 (PF3D7_1017400). We confirmed the PMM and phosphoglucomutase activities of purified recombinant HAD5 by developing novel linked enzThe Journal of biological chemistryEnzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria-causing parasites.PMC8808168R21 AI144472R61 HD105594R21 AI123808153332R01 AI103280R61 DH105594R21 AI13058403893-2020Zhu JSGoldberg DEOdom John ARFrasse PMSoleimani EMiller JJPolino AJJez JMJakeman DLfalseEnzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria-causing parasites.The malaria-causing parasite Plasmodium falciparum is responsible for over 200 million infections and 400,000 deaths per year. At multiple stages during its complex life cycle, P. falciparum expresses several essential proteins tethered to its surface by glycosylphosphatidylinositol (GPI) anchors, which are critical for biological processes such as parasite egress and reinvasion of host red blood cells. Targeting this pathway therapeutically has the potential to broadly impact parasite development across several life stages. Here, we characterize an upstream component of parasite GPI anchor biosynthesis, the putative phosphomannomutase (PMM) (EC 5.4.2.8), HAD5 (PF3D7_1017400). We confirmed the PMM and phosphoglucomutase activities of purified recombinant HAD5 by developing novel linked enz2022-01-01T00:00:00Z2022 Feb2026-05-30T15:17:03.186Z2024-10-18T17:10:12.527ZS-EPMC88081683497333310.1016/j.jbc.2021.101550