β-Propeller structure of the CJ1041C protein from Campylobacter jejuni and its interaction with Ca²⁺ ions

Campylobacter jejuni is the leading bacterial cause of foodborne enteric disease worldwide. The increasing emergence of antibiotic-resistant C. jejuni strains underscores the need to identify new protein targets for antibacterial drug development through the functional characterization of previously unstudied C. jejuni proteins. One such protein whose function has not been experimentally investigated is CJ1041C. To gain insight into the role of CJ1041C, we determined its crystal structures in both the apo form and in complex with Ca²⁺ ions. CJ1041C adopts a six-bladed β-propeller architecture, in which six four-stranded β-sheets are radially arranged around a central channel. This channel is occluded in the middle and harbors two oppositely oriented, negatively charged cavities. Notably, the upper cavity coordinates a Ca²⁺ ion through highly conserved residues and additionally accommodates a glycerol molecule presumably as a substrate-water mimic. The Ca²⁺-binding configuration of CJ1041C closely resembles that observed in β-propeller lactonases, suggesting that CJ1041C functions as a lactonase or lactonase-like enzyme. However, the unique glycerol-binding mode of CJ1041C, combined with the results of phylogenetic and sequence analyses, indicates that CJ1041C represents a distinct member of the β-propeller lactonase family that likely exerts catalytic activity toward noncanonical substrates.