Structural Superimposition

Abstact

Orotidine-5'-phosphate decarboxylase (OMP decarboxylase; ODCase) catalyzes a key step in de novo pyrimidine biosynthesis by converting orotidine-5'-monophosphate to uridine-5'-monophosphate. Despite its essential metabolic role, the structural basis underlying substrate recognition and binding dynamics in ODCase from Fusobacterium nucleatum (FnODCase) remains poorly understood. In the present study, we determined the crystal structure of FnODCase at 1.76 A resolution in the P 1 2(1) 1 space group, with R(work) and R(free) values of 0.21 and 0.23, respectively. To investigate the ligand specificity of FnODCase, we performed isothermal titration calorimetry using three nucleotides that share a pyrimidine ring: cytidine 5'-monophosphate, thymidine 5'-monophosphate, and uridine 5'-monophosphate. The ITC data showed that FnODCase selectively recognized only UMP, confirming its high specificity for the uridine moiety. Notably, structural comparisons between the apo form and UMP-bound models revealed potential conformational changes in the loop regions surrounding the active site. These structural insights are expected to inform the future development of selective antimicrobial agents against F. nucleatum.