Factors that distort the heme structure in Heme-Nitric Oxide/OXygen-Binding (H-NOX) protein domains. A theoretical...

DFT and dispersion-corrected DFT calculations were carried out to probe the factors that distort the heme structure in Heme-Nitric oxide/OXygen-binding (H-NOX) protein domains. Various model systems that include heme, heme+surrounding residues, and heme+surrounding residues+additional protein environment were examined; the latter system was calculated with a quantum mechanics/molecular mechanics (QM/MM) method. The computations were extended to a myoglobin (Mb) protein, in which the heme structure is quite planar, in contrast to that in H-NOX. The natural tendency of the heme is to be planar. The strong structural distortion in H-NOX is mainly brought about by the intermolecular interactions between the whole heme molecule (heme ring plus its peripheral substituents) and the surrounding residues, among which the polar residues (Tyr140, Pro115, Mse98) play major roles in distorting the heme structure. The two peripheral propionate substituents that are oriented on the same side of the heme plane can also make the molecule distort, but the distortion caused by this factor is not significant. In Mb, the surrounding residues considered are all nonpolar and do not cause a structural distortion. The different structural features of the heme macrocycle in the different proteins (H-NOX and Mb) are reproduced by the calculations. The dispersion correction is necessary, since it improves the calculated structures. The effects of the distortion on the binding affinity of the axial ligand to the heme were also examined.