Novel structure-activity relationships in bacterial hemoglobins

SMULEVICH, GIULIETTA; NICOLETTI, FRANCESCO P.; DROGHETTI, ENRICA; HOWES, BARRY D.; BUSTAMANTE, JUAN PABLO; ESTRIN, DARÍO; FEIS, ALESSANDRO; BOFFI, ALBERTO

Congreso; 24th International Conference on Raman Spectroscopy; 2014

The truncated hemoglobin of Thermobifida fusca (Tf-trHb) displays genuine peroxidase activity and contains a highly polar distal heme cavity in which TrpG8, TyrCD1, and TyrB10 provide three potential H-bond interactions to stabilize incoming ligands. The role of these residues has been recently addressed by studying their interaction with different exogenous ligands such as CO, F-, HS-, and OH-. The application of UV-Vis, RR, and EPR spectroscopy together with MD simulations of the wild-type and selected mutants has demonstrated that the various ligands are stabilized differently by H-bonds with the polar residues and water molecules. Moreover, the different capability of the TyrB10 and TyrCD1 residues to act as hydrogen bond donor or acceptor is fundamental in the process of ligand binding. In particular, a deprotonated TyrB10 can act as a proton acceptor and may facilitate the peroxidase activity, mimicking the role played by the distal His in heme containing peroxidases.