Skip to main content
Publications of the Week

Crystal Structure of an Intramembranal Phosphatase Central to Bacterial Cell-Wall Peptidoglycan Biosynthesis and Lipid Recycling

By April 2, 2018No Comments

Read the Publication

 This week we profile a recent publication in Nature Communications from
Dr. Natalie Strynadka
and Sean Workman (pictured) at the UBC Life Sciences Institute .

Can you provide a brief overview of your lab’s current research focus?

 In the Strynadka lab, our primary focus is to address the growing threat of antibiotic resistance through the structure-based design of inhibitors that either block existing antibiotic resistance mechanisms, or provide novel therapies by targeting proteins and macromolecular assemblies essential to bacterial viability or pathogenesis.

What is the significance of the findings in this publication?

Undecaprenyl pyrophosphate phosphatase (UppP) is an integral membrane protein that recycles the lipid carrier essential to the ongoing biosynthesis of the bacterial cell wall. While deletion of the uppP gene is not lethal in vitro, its absence in vivo results in a significant decrease in virulence in mouse models of infection, making it a promising target for the development of novel antibacterial therapies. Our high-resolution crystal structure revealed the mechanistic basis for UppP’s intramembranal phosphatase activity and substrate specificity. In addition, the presence of an inverted repeat topology, primarily found in channels and transporters, hints that UppP could be functioning as a phosphatase activated flippase to move the lipid carrier from the periplasmic leaflet to the cytoplasmic leaflet of the bacterial membrane.

What are the next steps for this research?

 First, we would like to obtain a co-structure of UppP with the lipid carrier to confirm our substrate docking experiments. After that, we are hoping to carry out functional studies to confirm or disprove that UppP has the ability to function as a specific carrier lipid flippase.

This research was funded by:

Sean D. Workman – Alexander Graham Bell Canada Graduate Scholarship from NSERC

Read the Publication