BIOINORGANIC CHEMISTRY A Short Course Second Edition

434 IRON-CONTAINING PROTEINS AND ENZYMES

case, a channel of polar atoms from subunits I and II amino acid side chains
would guide the water molecules to a cytosolic side (intermembrane space)
opening. Overall, cytochrome c oxidase must have a pathway for electron
movement and channels to move protons, dioxygen, and water molecules into
and out of the enzyme complex.

7.8.3 Dioxygen Binding, Proton Translocation, and Electron Transport

In all cytochrome c oxidase enzymes, O 2 is reduced at the bimetallic heme a 3 –
Cu B site. Several theories have been put forward to explain the trajectory of
electrons through the enzyme. Two of these, the fully reduced and the mixed
valence models, are graphically illustrated in Figure 7.40 and in Figure 11 of
reference 140.^140
In the fully reduced model, four electrons are transferred to dioxygen
through sequential one - electron oxidations of heme a 3 ’ s iron ion, the Cu B ion,
the heme a iron ion, and one of the bimetallic center ’ s Cu A ions. The sequence
of electron transferal differs in the mixed valence model, and a tyrosine radical
(tyr) is generated. The proposed formation of a tyrosine radical during cata-
lytic turnover arises from the known post - translational modifi cation in most
CcO ’ s in which a covalent bond is formed between the his240 ligand of Cu B

Figure 7.40 The cytochrome c oxidase reaction cycle starting from the mixed - valence
state.

A

R

mixed valence state

CuAI-CuAII

heme a FeIII

8-10μs O 2 binding

CuAI-CuAII

heme a FeIII

170-200μs

O-O bond cleavage

formation oxo-ferryl state at heme a 3

internal pT at catalytic site (H transfer

from YOH to CuB(I) and formation of

tyrosine radical)

CuAI-CuAII

heme a FeIII

FeII

heme a 3

heme a 3

FeII O

O

YO

.

HO CuBII

heme a 3

FeIVO2-

CuBI

YOH

CuBI λ = ~595 nm

ν(FeII- O) = 571 cm-1

λ = ~607 nm

ν(FeIV=O) = 803 cm-1

YOH

PM