Uridine Bisphosphonates Differentiate Phosphoglycosyl Transferase Superfamilies.

ABSTRACT: Complex bacterial glycoconjugates drive interactions between pathogens, symbionts, and their human hosts. Glycoconjugate biosynthesis is initiated at the membrane interface by phosphoglycosyl transferases (PGTs), which catalyze the transfer of a phosphosugar from a soluble uridine diphosphosugar (UDP-sugar) substrate to a membrane-bound polyprenol-phosphate (Pren-P). The two distinct superfamilies of PGT enzymes (polytopic and monotopic) show striking differences in their structure and mechanism. We designed and synthesized a series of uridine bisphosphonates (UBPs), wherein the diphosphate of the UDP and UDP-sugar is replaced by a substituted methylene bisphosphonate (CXY-BPs; X/Y = F/F, Cl/Cl, (S)-H/F, (R)-H/F, H/H, CH₃/CH₃). UBPs and UBPs incorporatin

SUBMITTER: Seebald LM 

PROVIDER: S-EPMC10922802 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature