Nitrous bases were shown to play an essential role in the specificity of active and adenyl nucleotide binding sites. Pyrimidine base determines the substrate specificity of rabbit skeletal muscle glycogen synthase; a crucial role in this process is ascribed to the lactam fragment of the pyrimidine cycle. The 2-oxo group was also shown to be involved in substrate binding. The adenyl nucleotide binding site interacts only with 6-aminopurine derivatives. A negative interaction was found between the enzyme active center and the adenyl nucleotide binding site.
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Nucleic Acids Res
January 2025
Department of Biochemistry, University of Zurich, Winterthurerstrass 190, 8057 Zurich, Switzerland.
Type III clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems (type III CRISPR-Cas systems) use guide RNAs to recognize RNA transcripts of foreign genetic elements, which triggers the generation of cyclic oligoadenylate (cOA) second messengers by the Cas10 subunit of the type III effector complex. In turn, cOAs bind and activate ancillary effector proteins to reinforce the host immune response. Type III systems utilize distinct cOAs, including cyclic tri- (cA3), tetra- (cA4) and hexa-adenylates (cA6).
View Article and Find Full Text PDFElife
January 2025
Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, United States.
The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.
View Article and Find Full Text PDFSheng Li Xue Bao
December 2024
College of Life Sciences, Anqing Normal University, Anqing 246133, China.
This study aimed to analyze the impact of single nucleotide polymorphism (SNP) of (encoding adenylate cyclase 3) on the outcome of high-intensity interval training (HIIT) on body composition and screen genetic markers sensitive to HIIT in Chinese Han youth. A total of 237 non-regular exercise Han college students were recruited in a 12-week HIIT program, attending sessions 3 times a week. Before and after the HIIT program, their body composition was measured.
View Article and Find Full Text PDFDevelopment
January 2025
Department of Biology, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Oscillatory dynamics and their modulation are crucial for cellular decision-making; however, analysing these dynamics remains challenging. Here, we present a tool that combines the light-activated adenylate cyclase mPAC with the cAMP biosensor Pink Flamindo, enabling precise manipulation and real-time monitoring of cAMP oscillation frequencies in Dictyostelium. High-frequency modulation of cAMP oscillations induced cell aggregation and multicellular formation, even at low cell densities, such as a few dozen cells.
View Article and Find Full Text PDFCommun Biol
December 2024
Department of Biochemistry, Groningen Biomolecular Science and Biotechnology Institute, University of Groningen, Nijenborgh 3, Groningen, The Netherlands.
Cyclic di-adenylate monophosphate (cyclic di-AMP) is an important second messenger in microorganisms. Cyclic di-AMP regulates bacterial cell volume and turgor via control of potassium and compatible solute transport but is also involved in many other processes, including the activation of the metazoan innate immune response to bacterial infections. We compare the activity of full-length membrane-embedded CdaA, the enzyme that synthesizes cyclic di-AMP, with the water-soluble catalytic domain CdaA-DAC.
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