Why Can Iron in Hemoglobin Make 6 Bonds?

[sameeralord]

Hello everyone,

I'm struggling a little bit to understand the structure of haemoglobin. I have few questions to ask.

1.Ok so the top bit must be the proximal histidine and in haemoglobin rather than water bottom bit is attached to distal histidine when oxygen is not present right? Now my question is why iron atom able to make 6 bonds. For example if it is oxygen, I know it has 6 electrons in final outershell so it need 2 electrons meaning 2 bonds. (I know energy levels are bit more complicated but this is my level at the moment). Using the same prinicple iron has 26 electrons, that mean it has 16 electrons in its furthest shell so I don't understand where 6 bonds are coming?
2. When the iron atom in heme group is attached to 6 bonds, is it just an iron atom, is it when it has only 4 bonds it becomes ferrous atom (Fe2+). I don't understand where Fe2+ is coming from. This is the picture I got from wikipedia that show heme group? Where is the Fe2+ atom and what is its importance?
[URL]http://upload.wikimedia.org/wikipedia/commons/4/4d/Heme.svg[/URL]
3. Is oxygen attached to the distal end of the histidine as well as the iron atom, or just the iron atom only?
4. What is the difference between tertiary structure and quaternary structure here? Is the 3 dimensional shape of 1 polypeptide chain called tertiary structure and many quaternary structure?

Thank you so much

 

[alxm]

Okay, well you're confusing coordination with bonding. Although I should immediately point out that there's no sharp line between the two, much as there's no sharp line between covalent and ionic bonding. Consider an Fe²⁺ ion in water. What does that look like? You have 6 water molecules octahedrally coordinated (4 in a plane around the Fe, one above, one below). The water molecules will orient such that the free electron pairs (relatively negative charge) are pointing towards the iron. This is coordination.

Now a heme is essentially a http://semicrystalline.files.wordpress.com/2007/05/porphyrin.jpg" group, where the two hydrogens in the middle have been replaced with an iron atom. So you can view it as the two negatively-charged nitrogen atoms forming ionic bonds to the positive iron, and the two neutral nitrogen atoms are just coordinating with their free electron pairs. The thing with porphyrins/hemes/cytochromes is that it's a completely aromatic structure. So you have resonance between which N's are bonding and which are coordinating. (exercise for the reader: draw the two resonance structures) So so you can view it as 'half' a bond from each nitrogen.

So in hemoglobin heme, which is usually Fe(II), the iron has two bonds from the heme group (which you can view as two binding and two coordinating, or all of them "half-binding"). The distal histidine is only coordinating, and so is the water.

Note that you still say Fe(II) even though it's accepting two negative charges from the heme! Note that there's no requirement that the whole thing be neutral, even though it happens to be in this case. Depending on the circumstances you could have anything from Fe(II) to Fe(V) there. (in other porphyrin-cofactor enzymes. Hemoglobin normally sticks with Fe(II), it's just a transporter, not a redox-active enzyme)

Hemoglobin binds molecular oxygen (O₂), not an oxygen atom, so it just coordinates as well. It can't bind to the histidine, it's nowhere near there (the oxygen binds 1.5-2 Å on one side of the plane of the heme, and the histidine is about as far on the other side, with the whole big porphyrin in-between) Also, why would oxygen bind to a nitrogen?

 

[Rajini]

Hello,
There are lots of articles available (do you have access, for eg., JACS, Phys. Rev. B, etc ?).
Oxidation state for 4 or 6 coordinate iron is usually +2 or +3.
For transition metals (in your case iron), only the 3d-electrons which participate in bonding. For iron it is 6 electrons and these electrons mostly define the spin-state of iron.
For Fe in +2 oxidation state you have 6 3d-electrons (spin-state may be S=0 or 1 or 2).
For Fe in +3 oxidation state you have 5 3d-electrons (spin-state may be S=5/2 or 3/2 or 1/2).
More over there are lots of porphyrin structures..to my knowledge either with 6 or 5 coordination for iron. So what you need is to please check about the oxidation, multiplicity and spin state of the iron and charge of the whole prophyrin molecule..

 

[Rajini]

Hello alxm,
may i know the charge of the whole porphyrin molecule without the central metal iron.
In this wiki link
http://en.wikipedia.org/wiki/Porphyrin
what is the whole charge of the porphyrin molecule (the first figure in that link)
thanks

is it -2??

 

[sameeralord]

Thanks for all the replies So is their a mistake in my biochemistry note. It says that when oxygen is not bound to heme, proximal histidine is bound to ferrous atom and other his residue involved (His-58 alpha and His 63 Beta) is also connected by a coordinate bond to the 6th valency of the ferrous atom. Alxm is that sentence wrong, is the distal histidine not attached to ferrous atom?

 

[alxm]

what is the whole charge of the porphyrin molecule (the first figure in that link) thanks
is it -2??

It's neutral in that picture. With a metal atom there it's -2. Imagine that you remove the two hydrogen atoms in the middle as H⁺ when substituting for a metal atom.

Hemoglobin is almost always Fe(II). (Under certain physiological conditions it can be oxidized to Fe(III) but this is not its main function.) It has an even number of valence electrons, and IIRC, it has a singlet state when water is bound (termed the 'low-spin state') and a triplet ('high spin') state otherwise. Yes, there's a huge amount of literature on the electronic structure of porphyrins and related compounds. I think there's a whole journal dedicated to porphyrins.

It says that when oxygen is not bound to heme, proximal histidine is bound to ferrous atom and other his residue involved (His-58 alpha and His 63 Beta) is also connected by a coordinate bond to the 6th valency of the ferrous atom. Alxm is that sentence wrong, is the distal histidine not attached to ferrous atom?

If it says that His-58 coordinates to the iron atom in deoxyhemoglobin, then that's incorrect. It's too far away to be able to do that. I don't think they're wrong though, I think they mean that His-58 coordinates to a water which in turn is bound to the site. I.e. the histidine is in the second coordination shell.

 

[Rajini]

All right alxm, thanks
for eg., in this paper doi:10.1021/ja038526h
they investigate a ferrous porphyrin nitrosyl. (in simple words iron is in 5 coordination, i.e. four N atoms and one NO.
Now the whole structure has net charge zero (iron in +2 and -2 for porphyrin) is this correct ? But why they say S=1/2 (page: 4215). To me for a ferrous means +2 so S can only be 0 or 1 or 2. Do i miss something.?

 

[alxm]

Now the whole structure has net charge zero (iron in +2 and -2 for porphyrin) is this correct ?

Yes, there are two propionate groups on heme/cytochrome as well, but those are usually or binding to an arginine or something. Not much effect on the iron center either way.

But why they say S=1/2 (page: 4215). To me for a ferrous means +2 so S can only be 0 or 1 or 2. Do i miss something.?

It's binding nitric oxide (NO), which is a radical.