Processivity in Bacterial Glycosyltransferases

ACS Chem Biol. 2020 Jan 17;15(1):3-16. doi: 10.1021/acschembio.9b00619. Epub 2019 Dec 11.

Abstract

Extracellular polysaccharides and glycoproteins of pathogenic bacteria assist in adherence, autoaggregation, biofilm formation, and host immune system evasion. As a result, considerable research in the field of glycobiology is dedicated to study the composition and function of glycans associated with virulence, as well as the enzymes involved in their biosynthesis with the aim to identify novel antibiotic targets. Especially, insights into the enzyme mechanism, substrate binding, and transition-state structures are valuable as a starting point for rational inhibitor design. An intriguing aspect of enzymes that generate or process polysaccharides and glycoproteins is the level of processivity. The existence of enzymatic processivity reflects the need for regulation of the final glycan/glycoprotein length and structure, depending on the role they perform. In this Review, we describe the currently reported examples of various processive enzymes involved in polymerization and transfer of sugar moieties, predominantly in bacterial pathogens, with a focus on the biochemical methods, to showcase the importance of studying processivity for understanding the mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacteria / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Biocatalysis / drug effects
  • Drug Design
  • Glycoproteins / chemistry
  • Glycoproteins / metabolism*
  • Glycosylation / drug effects
  • Glycosyltransferases / metabolism*
  • Humans
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*
  • Signal Transduction
  • Structure-Activity Relationship
  • Virulence

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Glycoproteins
  • Polysaccharides
  • Glycosyltransferases