Bacterial glycogen synthases transfer a glucosyl unit, retaining the anomeric configuration, from ADP-glucose to the non-reducing end of glycogen. We modeled the Escherichia coli glycogen synthase based on three glycosyltransferases with a GT-B fold. Comparison between the model and the structure of the active site of crystallized retaining GT-B glycosyltransferases identified conserved residues with the same topology. To confirm the importance of these residues predicted by the model, we studied them in E. coli glycogen synthase by site-directed mutagenesis. Mutations D137A, R300A, K305A, and H161A decreased the specific activity 8100-, 2600-, 1200-, and 710-fold, respectively. None of these mutations increased the Km for glycogen and only H161A and R300A had a higher Km for ADP-Glc of 11- and 8-fold, respectively. These residues were essential, validating the model that shows a strong similarity between the active site of E. coli glycogen synthase and the other retaining GT-B glycosyltransferases known to date.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2004.02.136 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Coumarin Analogues as Promising Anti-Obesity Agents: In Silico Design, Synthesis, and In Vitro Pancreatic Lipase Inhibitory Activity.
Chem Biol Drug Des
January 2025
Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS Pilani), Pilani, Rajasthan, India.
A set of coumarin-3-carboxamide analogues were designed, synthesized, and evaluated for their ability to impede pancreatic lipase (PL) activity. Out of all the analogues, 5dh and 5de demonstrated promising inhibitory activity against PL, as indicated by their respective IC values of 9.20 and 11.
View Article and Find Full Text PDFPyridine Derivatives and Furan Derivatives Identified from the Medicinal Mushroom Irpex lacteus SY1002.
Chem Biodivers
January 2025
Qingdao Agricultural University, School of Life Sciences, Qingdao, CHINA.
Three new pyridine derivatives, irpelactedines A-C (1-3), and a new furan derivative, irpelactedine D (5), along with two structurally related known compounds, irpexidine A (4) and 5-carboxy-2-furanpropanoic acid (6), were isolated from the medicinal fungus Irpex lacteus SY1002. Their structures were elucidated through NMR and mass spectral analyses, combined with density functional theory calculations of ECD data. Evaluation of angiotensin-converting enzyme (ACE) inhibitory activity revealed that compounds 1 and 3 displayed moderate inhibition, with IC50 values of 31.
View Article and Find Full Text PDFInsights into the flexibility of the domain-linking loop in actinobacterial coproheme decarboxylase through structures and molecular dynamics simulations.
Protein Sci
February 2025
Department of Chemistry, Institute of Biochemistry, BOKU University, Vienna, Austria.
Prokaryotic heme biosynthesis in Gram-positive bacteria follows the coproporphyrin-dependent heme biosynthesis pathway. The last step in this pathway is catalyzed by the enzyme coproheme decarboxylase, which oxidatively transforms two propionate groups into vinyl groups yielding heme b. The catalytic reaction cycle of coproheme decarboxylases exhibits four different states: the apo-form, the substrate (coproheme)-bound form, a transient three-propionate intermediate form (monovinyl, monopropionate deuteroheme; MMD), and the product (heme b)-bound form.
View Article and Find Full Text PDFCryo-EM SPR structures of Salmonella typhimurium ArnC; the key enzyme in lipid-A modification conferring polymyxin resistance.
Protein Sci
February 2025
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.
View Article and Find Full Text PDFEfficacy and safety of PCSK9 inhibitors in real life.
Clin Investig Arterioscler
January 2025
Unidad de Lípidos y Riesgo Vascular, Servicio de Endocrinología y Nutrición, Hospital del Mar, Barcelona, España. Electronic address:
Objective: To confirm the effectiveness and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in daily clinical practice.
Methods: Retrospective observational study of patients from hospital registry of PCSK9 inhibitor treatment with a follow-up ≥ 6 months. The lipid-lowering effect and safety were evaluated.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!