Synergistic computational and experimental studies of a phosphoglycosyl transferase membrane/ligand ensemble

Specificity determinants revealed by the structure of glycosyltransferase Campylobacter concisusPglA

“…In a number of species from Campylobacter and Helicobacter genera, including the important human pathogens, Campylobacter jejuni and Campylobacter concisus (Dasti et al, 2010;Javed et al, 2017;Kaakoush & Mitchell, 2012;Liu et al, 2018), the N-linked glycoconjugates are synthesized in a stepwise manner via the pgl biosynthetic pathway (Figure 1). The orientation of undecaprenol phosphate mirrors that determined through molecular dynamics simulation, suggesting its residence within a single leaflet of the lipid bilayer (Majumder et al, 2023). Following the first membrane-committed step in the pathway which transfers a phospho-N,N 0 -diacetylbacillosamine (phospho-diNAcBac) to undecaprenol phosphate (UndP) by the phosphoglycosyl transferase PglC (Jervis et al, 2012;Ray et al, 2018), the membrane-associated glycosyltransferases PglA, PglJ, PglH, and PglI catalyze the stepwise addition of sugar moieties to form a heptasaccharide.…”

Machine Learning Derived Collective Variables for the Study of Protein Homodimerization in Membrane

“…Most membrane proteins contain one or more transmembrane (TM) regions that span the membrane bilayer. 1,2 Membrane proteins also play crucial roles in cellular signaling with G-protein coupled receptors representing common therapeutic targets. 3 Association of membrane associated enzymes and their substrates through the interaction of the TM domains is known to play a key role in the biogenesis of a diverse array of proteins including the amyloidβ (Aβ) protein in Alzheimer's disease.…”

“…Membrane proteins represent an important class of biomolecules that are essential to cellular organization and function. Most membrane proteins contain one or more transmembrane (TM) regions that span the membrane bilayer. , Membrane proteins also play crucial roles in cellular signaling with G-protein coupled receptors representing common therapeutic targets . Association of membrane associated enzymes and their substrates through the interaction of the TM domains is known to play a key role in the biogenesis of a diverse array of proteins including the amyloid-β (Aβ) protein in Alzheimer’s disease. , As a result, the association of TM regions of the protein in membrane has received significant attention in experiment, theory, and simulations for over four decades. − Nevertheless, there remain fundamental outstanding questions related to the nature of the associated state and the magnitude of related equilibrium association constants.…”