Effects of distal mutation on the dynamic properties of carboxycytoglobin: a molecular dynamics simulation study.

Cytoglobin (Cgb) is a hexacoordinate globin that plays various physiological roles, including O2 transport, enzyme activity, and lipid peroxidation. The distal His(81)(E7) residue acts as the native sixth ligand and is crucial to exogenous ligand binding, distal environment adjustment, and heme pocket stabilization. The role of E7 has been widely studied in myoglobin, neuroglobin, and hemoglobin, but not in Cgb. In this work, the structural dynamic features of CO-ligated Cgb, CgbCO, as well as its three distal mutants H81QCgbCO, H81LCgbCO, and H81VCgbCO, were examined by performing molecular dynamics (MD) simulations. Results revealed that distal mutation significantly affected the dynamic properties of the CD-D-E and EF loop regions of Cgb. Distinct fluctuations and the occurrence of new inner cavities reflected rearrangements of the heme pocket. Distal mutation was found to affect heme motion slightly, indicating a different heme motion mechanism than that for neuroglobin. Some key residues such as E7 and CD3 showed remarkable changes in their dynamics that contributed to heme pocket rearrangement and loop region fluctuations. MD studies of four CgbCO models indicated that the distal E7 residue was a crucial influence on the dynamics of CgbCO in terms of loop fluctuations, cavity rearrangement, and slight heme motion.