Heme Cofactors

Here are the basic structures of tetrapyrrole cofactors, you will need to know how to draw these for the final. The most common is the porphyrin, which is found in most of the enzymes we will talk about. The chlorins are formed by reduction of one of the pyrrole rings; this is the structure of many of the cofactors involved in light-harvesting by green plants. The reduction of the pyrrole leads to a looser, less planar structure. The corrin ring is found in the B-12 cofactor cobalamin, it is not aromatic but retains the 4 N square planar coordination of the metal. Corrins are MUCH more flexible than porphyrins, and that is important in the way cobalamins work!

Practice drawing these before the FINAL!!

The reactivity of the heme cofactors are also influenced by the axial coordination of the metals:

Myoglobin and Hemoglobin have one axial histidine, N-bound to the Fe in the proximal pocket. The other axial site, in the distal pocket, is where dioxygen binds in the active FeII forms of these proteins. In the inactive FeIII forms, water or other aqueous ligands are bound to the Fe in the distal pocket.

Peroxidases, which oxidize substrates by reacting with peroxide, also have a single histidine axial ligand. Shown is a xtal structure of Horseradish Peroxidase. The active form is FeIII, which reacts with peroxide forming a highly oxidizing intermediate that has a O=Fe(IV) ferryl, with a second oxidizing equivalent as a porphyrin cation-radical.

In the Cytochromes P450, the axial ligand is a thiolate anion, RS-, formed from Cysteine. This protein also forms a O=Fe(IV) intermediate with a protein radical, upon reduction of an O2-adduct of the FeII form. The resting form has a water bound to FeIII.

Learn the ligation of the Fe sites in myoglobin, peroxidase, P450 proteins in both Fe(II) and Fe(III) forms: