Chapter 4. Metal Cofactors

• Heme c is linked covalently to the protein via two thioether Cys groups
• Heme P460 is attached to the protein matrix via 2 thioether linkages like Cytochrome c; also there is an additional linkage of Tyr
• Heme a (cytochrome c oxidase) and heme o have afarnesylhydroxylethyl side chain; heme a also has a formyl group at position 8
• Heme d1 has unconjugated A and B rings
• Siroheme like heme d1 has unconjugated A and B rings and additional propionate side chains
• The heme iron is bound to the Fe-PPIX cofactor which is (-2) charged; the -2 charge is shared by the 4 pyrrole N’s by resonance
• The possible oxidation states for heme are Fe3+ and Fe2+
• Available spin states (octahedral, two over three):

  High spin Fe3+(S = 5/2) or low-spin Fe3+(S = 1/2)

  High spin Fe2+(S = 2) or low-spin Fe2+(S = 0)
• The heme iron is typically 5-coordinate or 6-coordinate with 1 or 2 axial ligands bound
• Weak Field Ligand = Small Gap

  Strong Field Ligand = Large Gap
• 5 Coordinate Heme:

  AA Ligands: Cys, Met, His, Tyr

  Has open spot for binding an small molecule
• 5 coordinate heme:

  Binding CO, O2, NO, CN- = low spin, six coordinate complex

  CO and O2 binds only to Fe 2+

  CN- binds only to Fe 3+
• 6 Coordinate hemes:

  Typically low spin (S = 1/2 or 0)
• For determining spin states,

  Heme = Octahedral

  Fe-S clusters = Tetrahedral
• A)Rubredoxins = Fe(Cys)4 and can dontate 1 electron

  B/C)Ferrodoxins and Rieske proteins = 2Fe-2S with 2 His ligands and donate 2 electrons

  D) 3Fe-4S cluster can donate 3 electrons

  E) 4Fe-4S cluster can donate 4 electrons