Modeling truncated hemoglobin vibrational dynamics

Abstract

We present a study on the near equilibrium dynamics of two small proteins in the family of truncated hemoglobins, developed under the framework of a Gaussian network approach. Effective beta carbon atoms are taken into account besides Calphas for all residues but glycines in the coarse-graining procedure, without leading to an increase in the degrees of freedom (beta Gaussian Model). Normalized covariance matrix and deformation along slowest modes with collective character are analyzed, pointing out anticorrelations between functionally relevant sites for the proteins under study. In particular, we underline the functional motions of an extended tunnel-cavity system running inside the protein matrix, which provide a pathway for small ligands binding with the iron in the heme group. We give a rough estimate of the order of magnitude of the relaxation times of the slowest two overdamped modes and compare results with previous studies on globins.

Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis

“…Finally, in line with previous studies carried out to identify the factors that modulate ligand migration in heme proteins, − these results point out that the dual-path ligand-induced dynamical regulation mechanism in trHbN relies on a small number of key residues. This finding opens challenging questions relative to the involvement of similar ligand diffusion mechanisms in other truncated hemoglobins, whose activity might be regulated by motional fluctuations of certain structural domains or even in the recently discovered neuroglobin and cytoglobin. − A particularly challenging case is trHbN of M. smegmatis , which has nearly 70% sequence similarity with trHbN of M. tuberculosis and retains most of the structural features crucial to attain the trHb fold . In fact, PheE15, TyrB10, and GlnE11 are retained, and the protein binds oxygen reversibly with high affinity.…”