Nkosana, Noreen K. published the artcileSynthesis, kinetics and inhibition of Escherichia coli Heptosyltransferase I by monosaccharide analogues of Lipid A, COA of Formula: C9H16O6, the main research area is drug resistance heptosyltransferase inhibition KDO ulosonic acid preparation; protein dynamic mechanism inhibition HepI enzyme antibiotic antibacterial; mol docking enzyme substrate inhibitor allosteric binding conformation; lipid monosaccharide Escherichia coli kinetic synthesis heptosyltransferase inhibition; Allosterism; AutoDock Vina; GT-B; Glycosyltransferase; Heptosyltransferase; Inhibition kinetics; Inhibitor design; LPS; Lipopolysaccharide; Structural rearrangement.
Gram-neg. bacteria comprise the majority of microbes that cause infections that are resistant to pre-existing antibiotics. The complex cell wall architecture contributes to their ability to form biofilms, which are often implicated in hospital-acquired infections. Biofilms promote antibiotic resistance by enabling the bacteria to survive hostile environments such as UV radiation, pH shifts, and antibiotics. The outer membrane of Gram-neg. bacteria contains lipopolysaccharide (LPS), which plays a role in adhesion to surfaces and formation of biofilms. The main focus of this work was the synthesis of a library of glycolipids designed to be simplified analogs of the Lipid A, the membrane embedded portion component of LPS, to be tested as substrates or inhibitors of Heptosyltransferase I (HepI or WaaC, a glycosyltransferase enzyme involved in the biosynthesis of LPS). Fourteen analogs were synthesized successfully and characterized. While these compounds were designed to function as nucleophilic substrates of HepI, they all demonstrated mild inhibition of HepI. Kinetic characterization of inhibition mechanism identified that the compounds exhibited uncompetitive and mixed inhibition of HepI. Since both uncompetitive and mixed inhibition result in the formation of an Enzyme-Substrate-inhibitor complex, mol. docking studies (using AutoDock Vina) were performed, to identify potential allosteric binding site for these compounds The inhibitors were shown to bind to a pocket formed after undergoing a conformational change from an open to a closed active site state. Inhibition of HepI via an allosteric site suggest that disruption of protein dynamics might be a viable mechanism for the inhibition of HepI and potentially other enzymes of the GT-B structural class.
Bioorganic & Medicinal Chemistry Letters published new progress about Allosterism. 2595-07-5 belongs to class alcohols-buliding-blocks, name is (2R,3R,4S,5R,6R)-2-(Allyloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, and the molecular formula is C9H16O6, COA of Formula: C9H16O6.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts