Comparative structural analysis of bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase from Bordetella pertussis and Bordetella parapertussis: a drug target against pertussis.

Bordetella pertussis and Bordetella parapertussis are Gram-negative, aerobic, and pathogenic bacteria and cause pertussis disease (whooping cough) in humans. Genomic island analysis indicated the presence of an important protein bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (BMD/MC) in both B. pertussis and B. parapertussis. BMD/MC is associated with carbon fixation, folate pathway, and microbial metabolism in a diverse environment. Sequence comparison analysis indicates two amino acid variations between BMD/MC of B. pertussis and B. parapertussis and this difference reflects a good extent of variation in their 3D model. After refinement, BMD/MC model assessment result shows that 96.77% residue of B. pertussis and 97.49% residues of B. pertussis belong to the favored region of the Ramachandran plot, indicating a good quality model. During structural alignment, chain A of BMD/MC for B. pertussis and B. parapertussis shows the RMSD of 0.058 angstroms between 281 pruned atom pairs. Cavity analysis predicts a single cavity with an area (362.723 Å2) and volume (216.631 Å3) in the BMD/MC of B. pertussis, whereas the area and volume of cavity in B. parapertussis is 479.689 Å2 and 350.982 Å3 respectively. Several residues in the predicted cavity of both organisms are common with a good extent of variation in their area and volume. The average value of RMSD, RMSF, the radius of gyration, and principal component analysis (eigenvectors) for the BMD/MC model (B. parapertussis) was found smaller as compared to B. pertussis, which indicates that the B. parapertussis model is comparatively better than B. pertussis. MDS analysis suggests that both modeled structures are stable, good quality, and a compact model with a small degree of motions.