STRUCTURAL DYNAMICS OF E.coli PORPHOBILINOGEN DEAMINASE DURING THE TETRAPOLYMERISATION OF PORPHOBILINOGEN

Porphobilinogen deaminase catalyses the formation of 1-hydroxymethylbilane through a step-wise polymerisation of four units of porphobilinogen using a unique dipyrromethane cofactor as a primer. Structural and biochemical studies have suggested residues with catalytic importance, but their specific role in the mechanism and the dynamic behaviour of the protein remains unknown. Dynamics of the protein through three stages of chain elongation were studied using MD simulations to understand the concomitant structural changes. Observations suggest that domain 1 and domain 2 move apart while the cofactor turn region (240-243) moves into the active site and is inclined towards domain 2, thus creating space for the pyrrole moieties added at each stage. Results also suggest possible role of D50, K55 and R149 in active site loop modulation.