‘It's hollow’: the function of pores within myoglobin

Abstract

SUMMARY Despite a century of research, the cellular function of myoglobin (Mb), the mechanism regulating oxygen (O2) transport in the cell and the structure–function relationship of Mb remain incompletely understood. In particular, the presence and function of pores within Mb have attracted much recent attention. These pores can bind to Xe as well as to other ligands. Indeed, recent cryogenic X-ray crystallographic studies using novel techniques have captured snapshots of carbon monoxide (CO) migrating through these pores. The observed movement of the CO molecule from the heme iron site to the internal cavities and the associated structural changes of the amino acid residues around the cavities confirm the integral role of the pores in forming a ligand migration pathway from the protein surface to the heme. These observations resolve a long-standing controversy – but how these pores affect the physiological function of Mb poses a striking question at the frontier of biology.

Myoglobin oxygen affinity in aquatic and terrestrial birds and mammals

“…Within the Mb protein are several highly conserved hydrophobic cavities oxygen partial pressure (mmHg) (Fig. 5), including the heme pocket, the distal pocket (DP) and four additional pockets (Xe1-Xe4) (Tomita et al, 2010). A porphyrin ring is present within the heme pocket and is stabilized by hydrophobic interactions with nonpolar amino acids.…”

Dynamics comparison of two myoglobins with a distinct heme active site

“…The presence and function of internal cavities in Mb have attracted much attention recently, in particular focused on swMb [22][23][24][25][26][27][36][37][38][39]. To provide cavity information for apMb, we analyzed the cavities in both close and open forms of apMb and compared to that in swMb with energy minimization and MD simulation.…”

“…More hydrophobic residues such as F28, F112 and F134 locate among the cavities in apMb, resulting in a lower connectivity of these cavities. These differences may be related to the ligand binding kinetics and migration pathways inside the protein [22][23][24][25][26][27][37][38][39].…”

Computational Investigation of O2Diffusion Through an Intra–molecular Tunnel in AlkB; Influence of Polarization on O2Transport

“…[19][20][21][22] A number of computational studies have been reported on the diffusion of O 2 through intra-molecular tunnels. [22][23][24][25][26][27][28][29] One possible approach to investigate the transport of these types of molecules involves standard MD simulation of ligand diffusion, which ideally requires a large number of independent replicate runs of several ns to attain adequate sampling (flooding simulation). 19,22 A second approach involves the determination of the potential of mean force (PMF).…”