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Chemical-guided SHAPE sequencing (cgSHAPE-seq) informs the binding site of RNA-degrading chimeras targeting SARS-CoV-2 5' untranslated region.
Nat Commun
January 2025
Department of Medicinal Chemistry, University of Kansas, Lawrence, USA.
One of the hallmarks of RNA viruses is highly structured untranslated regions (UTRs) which are often essential for viral replication, transcription, or translation. In this report, we discovered a series of coumarin derivatives that bind to a four-way RNA helix called SL5 in the 5' UTR of the SARS-CoV-2 RNA genome. To locate the binding site, we developed a sequencing-based method namely cgSHAPE-seq, in which an acylating probe was directed to crosslink with the 2'-OH group of ribose at the binding site to create read-through mutations during reverse transcription.
View Article and Find Full Text PDFMutational analysis of an antimalarial drug target, ATP4.
Proc Natl Acad Sci U S A
January 2025
Department of Microbiology and Immunology, Center for Molecular Parasitology, Drexel University College of Medicine, Philadelphia, PA 19129.
Among new antimalarials discovered over the past decade are multiple chemical scaffolds that target P-type ATPase (ATP4). This essential protein is a Na pump responsible for the maintenance of Na homeostasis. ATP4 belongs to the type two-dimensional (2D) subfamily of P-type ATPases, for which no structures have been determined.
View Article and Find Full Text PDFNo Bridge between Us: EXAFS and Computations Confirm Two Distant Iron Ions Comprise the Active Site of Alkane Monooxygenase (AlkB).
J Am Chem Soc
January 2025
Department of Chemistry, Barnard College, 3009 Broadway, New York, New York 10027, United States.
Alkane monooxygenase (AlkB) is the dominant enzyme that catalyzes the oxidation of liquid alkanes in the environment. Two recent structural models derived from cryo-electron microscopy (cryo-EM) reveal an unusual active site: a histidine-rich center that binds two iron ions without a bridging ligand. To ensure that potential photoreduction and radiation damage are not responsible for the absence of a bridging ligand in the cryo-EM structures, spectroscopic methods are needed.
View Article and Find Full Text PDFFunctional Role of Odorant-Binding Proteins in Response to Sex Pheromone Component 8-14:Ac in (Busck).
Insects
November 2024
Shaanxi Province Key Laboratory of Jujube, College of Life Science, Yan'an University, Yan'an 716000, China.
The plum fruit moth (PFM), , and the oriental fruit moth (OFM), , are closely related fruit moth species that severely damage fruit trees in Rosaceae. Both species share common primary sex pheromone components 8-12:Ac and 8-12:Ac. The secondary sex pheromone components of PFMs consist of 8-12:OH, 8-14:Ac, and 10-14:Ac, while those of OFMs include 8-12:OH and 12:OH.
View Article and Find Full Text PDFCharacterization and PCR Application of Family B DNA Polymerases from .
Life (Basel)
November 2024
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, Russia.
DNA polymerases from the hyperthermophilic Archaea have attracted considerable attention as PCR enzymes due to their high thermal stability and proofreading 3' → 5' exonuclease activity. This study is the first to report data concerning the purification and biochemical characteristics of the Tst DNA polymerase from . Both the wild type Tst(wt) DNA polymerase and its chimeric form containing the P36H substitution-which reduces the enzyme's affinity for the U-containing template and dUTP-and the DNA-binding domain Sso7d from were obtained and analyzed.
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