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Impact of Ligand-Induced Oligomer Dissociation on Enzyme Diffusion, Directly Observed at the Single-Molecule Level.
Nano Lett
January 2025
Chemical Biology 1, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
The existence of the phenomenon of enhanced enzyme diffusion (EED) has been a topic of debate in recent literature. One proposed mechanism to explain the origin of EED is oligomeric enzyme dissociation. We used mass photometry (MP), a label-free single-molecule technique, to investigate the dependence of the oligomeric states of several enzymes on their ligands.
View Article and Find Full Text PDFConvergent evolution of oxidized sugar metabolism in commensal and pathogenic microbes in the inflamed gut.
Nat Commun
January 2025
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA.
Inflammation-associated perturbations of the gut microbiome are well characterized, but poorly understood. Here, we demonstrate that disparate taxa recapitulate the metabolism of the oxidized sugars glucarate and galactarate, utilizing enzymatically divergent, yet functionally equivalent, gud/gar pathways. The divergent pathway in commensals includes a putative 5-KDG aldolase (GudL) and an uncharacterized ABC transporter (GarABC) that recapitulate the function of their non-homologous counterparts in pathogens.
View Article and Find Full Text PDFPhysiological consequences of Aldolase C deficiency during lactation.
PLoS One
December 2024
Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
The lactating mammary gland strongly induces de novo lipogenesis (DNL) to support the synthesis of fatty acids, triglycerides, and cholesterol found within milk. In monogastric species, glucose is a major substrate utilized for DNL within the lactating mammary gland and must be efficiently taken up and processed to supply cytosolic acetyl-CoA for DNL. Along with the enzymes of the DNL pathway, the glycolytic enzyme, Aldolase C (Aldoc), is transcriptionally upregulated and is highly expressed during lactation in the mammary gland, suggesting a role for Aldoc in lactation.
View Article and Find Full Text PDFGlobal initiatives aim to curb tuberculosis (TB) by developing efficient vaccines and drugs against Mycobacterium tuberculosis (M. tb). The pressing need for innovative and swift anti-TB drug screening methods, due to the drawbacks of traditional approaches, is met by employing Structure-based virtual screening (SBVS) and machine learning (ML) in drug discovery.
View Article and Find Full Text PDFA recombinant L-threonine aldolase with high catalytic efficiency for the asymmetric synthesis of L-threo-phenylserine and L-threo-4-fluorophenylserine.
Biotechnol Lett
December 2024
Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China.
Objectives: To develop robust variants of L-threonine aldolases (L-TAs), potent catalysts for synthesizing asymmetric β-hydroxy-α-amino acids, it is necessary to identify critical residues beyond the known active site residues.
Results: Through virtual screening, a neglected residue Asn305, was identified as critical for catalytic efficiency. Subsequent site-saturation mutagenesis led to a potent variant N305R which exhibited excellent conversions of 88% (87%) and 80% (94%) for the synthesis of L-threo-phenylserine and L-threo-4-fluorophenylserine respectively.
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