I always think of a heme cofactor with bound iron as a flat molecule. However, after reparameterizing heme without iron for the purpose of an MD simulation, the cofactor demonstrates quite a degree of flexibility, notably around the carbon bonds which keep the four imidazole rings bound into the four-imidazole ring structure. I imagine, the presence of Fe would keep the four nitrogens planar, but in its absence, the negative charge on each nitrogen atom may cause each imidazole to rotate slightly.
I'm struggling to find an experimental structure of heme (and not any associated protein). Any suggestion?
I've attached a few images (same time frame from a top-down and side-on perspective) of a simulation based on a homology model from a crystal structure which included this particular heme group bonded-arrangement.
Thanks
Dear Anthony,
You may check the following links which contain x-ray structures of cytochromes:
1-Crystal structure of cytochrome C from bovine heart at 1.5 A resolution
http://www.rcsb.org/pdb/explore.do?structureId=2b4z
2-X-ray crystal structure of the cytochrome P450 2B4 active site mutant F297A in complex with clopidogrel: insights into compensatory rearrangements of the binding pocket.
https://www.ncbi.nlm.nih.gov/pubmed/23296089
Hoping this will be helpful,
Rafik
Hi Rafik,
Thanks for those links. Having looked at those x-ray structures, the heme groups seem very planar, a consequence of having an iron bound. I read somewhere (trying to find the source), that when molecular oxygen coordinates, the iron displaces, causing the heme group to curve. Any thoughts on how the group would look without iron?
Thanks
Dear Anthony,
Heme Coordination
Heme is a porphyrin that is coordinated with Fe(II). One of the most important classes of chelating agents in nature are the porphyrins. A porphyrin molecule can coordinate to a metal using the four nitrogen atoms as electron-pair donors. In the body, the iron in the heme is coordinated to the four nitrogen atoms of the porphyrin and also to a nitrogen atom from a histidine residue, one of the amino-acid residues in hemoglobin) of the hemoglobin proteins. The sixth protein, coordination site, around the iron of the heme is occupied by O2 when the hemoglobin is oxygenated. The heme group is nonplanar when it is not bound to oxygen. The iron is pulled out of the plane of the porphyrin, towards the histidine residue to which it is attached. This nonplanar configuration is characteristic of the deoxygenated heme group, and is often referred to as being "domed shape". When the Fe heme group binds to an oxygen molecule, the porphyrin ring adopts a planar configuration and hence the Fe lies in the plane of the porphyrin ring. Oxygenated and deoxygenated conformation of Hemoglobin
As may be seen in the figure, the left shows representations of electron-density clouds of the de-oxygenated heme group, depicted in pink, and the attached histidine residue which may be seen in light blue. These regions of electron density repel each other, and the iron atom in the center is drawn out of the plane. They non planar shape of the heme group is represented by the bent line. The right image depicts the electron-density clouds of the oxygenated heme group, shown in pink, the attached histidine residue in light blue, and the attached oxygen molecule which is shown in gray. The oxygenated heme assumes a planar configuration, and the central iron atom occupies a space in the plane of the heme group which is depicted by a straight red line.
Heme Group Shape
The shape change in the heme group also has important implications for the rest of the hemoglobin protein. When the iron atom moves into the porphyrin plane upon oxygenation, the histidine residue to which the iron atoms is attached to is drawn closer to the heme group. This movement of the histidine residue then shifts the position of other amino acids that are near the histidine. When the amino acids in a protein are shifted in this manner by the oxygenation of one of the heme groups in the protein, the structure of the interfaces between the four subunits is altered. So when a single heme group in the hemoglobin protein becomes oxygenated, the whole protein changes its shape. In the new shape, it is easier for the other three heme groups to become oxygenated. The binding of one molecule of oxygen to hemoglobin enhances the ability of hemoglobin to bind more oxygen molecules. This property of hemoglobin is known as "cooperative binding".
https://en.wikibooks.org/wiki/Structural_Biochemistry/Protein_function/Heme_group
The publication in the following link describes among other things, the structure properties of the heme in hemoglobin with and without an oxygen:
http://web.stanford.edu/~kaleeg/chem32/hemo/
You may also see relevant publications by J.P. Colleman who worked intensively in this field.
Hoping this will be helpful,
Rafik
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