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Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity.
ACS Infect Dis
January 2025
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, United States.
Half the world's population is at risk of developing a malaria infection, which is caused by parasites of the genus . Currently, resistance has been identified to all clinically available antimalarials, highlighting an urgent need to develop novel compounds and better understand common mechanisms of resistance. We previously identified a novel tetrahydro-β-carboline compound, PRC1590, which potently kills the malaria parasite.
View Article and Find Full Text PDFChirality-Induced Hydroxyapatite Manipulates Enantioselective Bone-Implant Interactions Toward Ameliorative Osteoporotic Osseointegration.
Adv Sci (Weinh)
December 2024
Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China.
Inspired by the fundamental attribute of chirality in nature, chiral-engineered biomaterials now represent a groundbreaking frontier in biomedical fields. However, the integration of chirality within inorganic materials remains a critical challenge and developments of chirality-induced bionic bone implants are still in infancy. In this view, novel chiral hydroxyapatite (CHA) coated Ti alloys are successfully synthesized by a sophisticated chiral molecule-induced self-assembly method for the first time.
View Article and Find Full Text PDF(-)-Swainsonine is a polyhydroxylated indolizidine alkaloid with potent inhibitory activity against α-D-mannosidases. In this work, we successfully reconstituted swainsonine biosynthetic pathway both in vivo and in vitro. Our study unveiled a surprising epimerization mechanism involving an imine reductase (SwnN) and two non-heme iron and α-ketoglutarate-dependent oxygenases (SwnH2 and SwnH1).
View Article and Find Full Text PDFHMGB3 and SUB1 Bind to and Facilitate the Repair of -Alkylguanine Lesions in DNA.
J Am Chem Soc
August 2024
Environmental Toxicology Graduate Program, University of California, Riverside, Riverside, California 92521-0403, United States.
-Alkyl-2'-deoxyguanosine (-alkyl-dG) is a major type of minor-groove DNA lesions arising from endogenous metabolic processes and exogenous exposure to environmental contaminants. The -alkyl-dG lesions, if left unrepaired, can block DNA replication and transcription and induce mutations in these processes. Nevertheless, the repair pathways for -alkyl-dG lesions remain incompletely elucidated.
View Article and Find Full Text PDFSeeing double: two different homospermidine oxidases are involved in pyrrolizidine alkaloid biosynthesis in different organs of comfrey (Symphytum officinale).
Plant J
August 2024
Botanical Institute and Botanic Gardens, Kiel University, Kiel, Germany.
Pyrrolizidine alkaloids (PAs) are toxic specialized metabolites produced in several plant species and frequently contaminate herbal teas or livestock feed. In comfrey (Symphytum officinale, Boraginaceae), they are produced in two different organs of the plant, the root and young leaves. In this study, we demonstrate that homospermidine oxidase (HSO), a copper-containing amine oxidase (CuAO) responsible for catalyzing the formation of the distinctive pyrrolizidine ring in PAs, is encoded by two individual genes.
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