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Structure-function analysis of carrier protein-dependent 2-sulfamoylacetyl transferase in the biosynthesis of altemicidin.
Nat Commun
December 2024
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
The general control non-repressible 5 (GCN5)-related N-acetyltransferase (GNAT) SbzI, in the biosynthesis of the sulfonamide antibiotic altemicidin, catalyzes the transfer of the 2-sulfamoylacetyl (2-SA) moiety onto 6-azatetrahydroindane dinucleotide. While most GNAT superfamily utilize acyl-coenzyme A (acyl-CoA) as substrates, SbzI recognizes a carrier-protein (CP)-tethered 2-SA substrate. Moreover, SbzI is the only naturally occurring enzyme that catalyzes the direct incorporation of sulfonamide, a valuable pharmacophore in medicinal chemistry.
View Article and Find Full Text PDFSystematic surveillance of SARS-CoV-2 reveals dynamics of variant mutagenesis and transmission in a large urban population.
Nat Commun
December 2024
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada.
Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we here deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of the Spike gene in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets.
View Article and Find Full Text PDFNeutral drift upon threshold-like selection promotes variation in antibiotic resistance phenotype.
Nat Commun
December 2024
Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, BC, Canada.
Heritable phenotypic variation plays a central role in evolution by conferring rapid adaptive capacity to populations. Mechanisms that can explain genetic diversity by describing connections between genotype and organismal fitness have been described. However, the difficulty of acquiring comprehensive data on genotype-phenotype-environment relationships has hindered the efforts to explain how the ubiquitously observed phenotypic variation in populations emerges and is maintained.
View Article and Find Full Text PDFHaplotype-Resolved Genotyping and Association Analysis of 1,020 β-Thalassemia Patients by Targeted Long-Read Sequencing.
Adv Sci (Weinh)
December 2024
Innovation Center for Diagnostics and Treatment of Thalassemia, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.
View Article and Find Full Text PDFUnraveling the Causal Relationship Between Blood Metabolites and Acne: A Metabolomic Mendelian Randomization Study.
J Cosmet Dermatol
January 2025
Department of Dermatology, Chinese People's Liberation Army Western Theater Command General Hospital, Chengdu, China.
Background: Acne is a common skin disorder that may be linked to metabolic dysfunction. However, the causal impact of blood metabolites on acne has not been thoroughly investigated.
Methods: We performed a metabolome-wide Mendelian randomization (MR) analysis on 486 blood metabolites and acne using a genome-wide association dataset.
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