Structural and Functional Analysis of Heparosan Synthase 2 from <i>Pasteurella multocida</i> (PmHS2) to Improve the Synthesis of Heparin.

ABSTRACT: Heparin is a widely used drug to treat thrombotic disorders in hospitals. Heparosan synthase 2 from Pasteurella multocida (PmHS2) is a key enzyme used for the chemoenzymatic synthesis of heparin oligosaccharides. It has both activities: glucosaminyl transferase activity and glucuronyl transferase activity; however, the mechanism to carry out the glyco-oligomerization is unknown. Here, we report crystal structures of PmHS2 constructs with bound uridine diphosphate (UDP) and a cryo-EM structure of PmHS2 in complex with UDP and a heptasaccharide (NS 7-mer) substrate. Using a LC-MC analytical method, we discovered the enzyme displays both a two-step concerted oligomerization mode and a distributive oligomerization mode depending on the non-reducing end of the starting oligosaccharide pr

SUBMITTER: Stancanelli E 

PROVIDER: S-EPMC11845225 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature