​Overview:

• Cayman’s Structural Biology service group worked with a client to perform crystallization studies that delivered multiple high-resolution crystal structures of LpxC, an enzyme involved in Gram-negative bacteria pathogenicity, bound with lead inhibitors.
  
• Thermal shift assay (TSA) protein formulation and cryoprotectant screening showed Mg²⁺ and tartrate to be effectively stabilizing for P. aeruginosa LpxC. Improved crystallization space and novel crystallization conditions were identified by TSA that enabled the co-crystallization of P. aeruginosa LpxC with inhibitor compounds.
  
• Crystal structures determined the key interactions of the inhibitors in the P. aeruginosa LpxC binding pocket. These findings led to the discovery of a prodrug with high solubility and rapid conversion to active drug upon i.v. administration to treat P. aeruginosa infections.
  
• The TSA-driven crystallization platform offered by Cayman enabled the client to rapidly advance their P. aeruginosa drug discovery program.