A Tour of Hemerythrin

Please be patient while the structures in the left frame load. In order to display all of the structures in the tour properly, press 'View' buttons below in order (from 1 to the end).

Hemerythrin is a respiratory protein found in nature among a few marine phyla, arthropods, molluscs, vertebrates and invertebrates. This protein functions as a reversible oxygen carrier. Hemerythrin is found in an octameric form displayed in the left frame.

The backbone of four of the eight subunits is shown in the left frame. As it can be seen, they all consist of four parallel alpha helices. Each of these subunits contain an active site that is able to bind one dioxygen molecule.

Hemerythrin has two iron ions (light brown) at the active site. They are both Fe(II) in the deoxy-hemerythrin and Fe(III) in oxy- hemerythrin. However, in certain cases a mixed valence state Fe(II)/Fe(III) can also exist.

The two iron ions are bridged by a hydroxyl group (coloured red). The hydrogen of the μ-hydroxo ligand is not located in X-ray studies but spectroscopic studies suggest the presence of µ-OH instead of µ-O. The Fe – O – Fe angle is around 110 degrees.

The active site is connected to the rest of the protein backbone at both iron ions. Three histidine residues, shown in blue (his73, his77 and his 101) are attached to the Fe1 atom. (The Fe-N bonds are not shown here because the Chime plug-in unfortunately does not show bonds between metals and the ligands when there are over 255 atoms in the display.)

However, only two histidine residues (grey, His54 and His25) are bonded to Fe2 ion.

Two additional ligands that bridge the irons are aspartate (Asp106, green) and glutamate (Glu58, magenta).

This is hemerythrin’s active site. We can see that Fe1 is six-coordinate and has an octahedral geometry. On the other hand, Fe2 is five-coordinate and has a distorted trigonal bipyramidal geometry. This asymmetrical coordination of the two Fe centers has important consequences. First, Fe2 is co-ordinately unsaturated and can coordinate additional ligands. Second, the Fe –O distances are not identical. The Fe2 – O distance is shorter than the Fe1 – O distance. (Check it for yourself by left-clicking on the pane at left and using the jmol menu).

This is hemerythrin’s active site after reaction with dioxygen. After the dioxygen molecule binds to the active site, Fe2 becomes six-coordinate. The hydrogen atom moves from the μ-HO group to the O2 ligand to form a hydroperoxy ligand (HOO-). The HOO group then forms a hydrogen bond with the newly-formed bridging oxo (μ-O) group. (This hydrogen atom is not located in the X-ray structure. Do you know why?) These changes are reversed when O2 is released.

This is the structure of oxyhemerythrin for you to explore further.

The structure of deoxy and oxy hermerythrin was reported by Holmes, M.A. et al. J. Mol. Biol. 218 (1991) 583 – 593. (PDB IDs: 1HMD and 1HMO for deoxy and oxy hemerythrin respectively).

Hemerythrin – Model Complex

In order to better understand the conversion of deoxy- to oxy- hemerythrin (the binding of dioxygen and its conversion to a hydroperoxy group via proton transfer), several simple model systems have been prepared

The synthesis of a complex that contains an Fe-(μ-OH)-Fe moiety in which one iron is five-coordinate while the other is six-coordinate presents a challenge that has not yet been met.

This is the structure of oxyhemerythrin for you to explore further. This is the structure of one of the complexes reported recently that mimics well the activity of hemerythrin.[1] The complex has two iron(II) ions bridged by a hydroxyl group (the hydrogen atom is not located in the X-ray study). A dicarboxylic acid acts as a tetradentate ligand. (If you would like to see the structure of this diacid click (To return to the prior display click 'View 10' button!) Additionally each iron is bonded to one dipyrrolidinoethane ligand as a bidentate N donor ligand. The sixth coordination site on one iron is occupied by a triflate ligand (CF3SO3-, usually abbreviated as OTf-). The second iron atom remains pentacoordinate. This complex reacts with dioxygen in the presence of N-methyl imidazole at –78 degrees to give an oxo-bridged diiron complex with a hydroperoxy ligand on one iron and an N-methyl imidazole on the other. The structure of the reaction product is supported by spectroscopic measurements but no crystal structure is available yet.

This is another complex that models the structure of the active site of hemerythrin [2]. In this case both of the irons are six-coordinate hence are not able to react with dioxygen. However, it contains a rather interesting ligand: hydridotris(1-pyrazolyl)borate ([HB(C3H3N2)3]-, usually abbreviated Tp) [3]. This ligand is often used in bioinorganic model complexes. Its structure is shown . (To return to the prior display click 'View 11' button!)

If you would like to learn more about the hemerythrin model compounds and their chemistry see:

and references therein.

div101 (1K)

[1] Mizoguchi, T.J. et al. Inorg. Chem. 40 (2001) 4662-4673

[2] Beer, R.H. et al. Inorg. Chem. 30 (1991) 2083 - 2092

[3] Trofimenko, S. Inorg. Synth. 12 (1970) 99

Copyright Robert H. Morris, Adrian Lee and Alen Hadzovic, 1998, 2009, 2011.