Monooxygenases

Metal-containing monooxygenase enzymes are known that contain heme iron, nonheme iron, or copper at their active sites. 2 For most of these enzymes, there is only limited information about the nature of the active site and the mode of interaction with dioxygen or substrates. But there are three monooxygenase enzymes that strongly resemble well-characterized reversible dioxygen-carrying proteins (see preceding chapter), suggesting that dioxygen binding to the metalloenzyme in its reduced state is an essential first step in the enzymatic mechanisms, presumably followed by other steps that result in oxygenation of substrates. The enzymes are:
 

1. cytochrome P-450,73 a heme-containing protein whose active site resembles the dioxygen-binding sites of myoglobin or hemoglobin in many respects, except that the axial ligand to iron is a thiolate side chain from cysteine rather than an imidazole side chain from histidine;
2. tyrosinase,74 which contains two copper ions in close proximity in its active site and which has deoxy, oxy, and met states that closely resemble comparable states of hemocyanin in their spectroscopic properties; 
3. methane monooxygenase,75,76 which contains two nonheme iron ions in close proximity and which resembles hemerythrin in many of its spectroscopic properties.

In addition to these three, there are also monooxygenase enzymes containing single nonheme iron 77 or copper ions,78 or nonheme iron plus an organic cofactor such as a reduced pterin at their active sites. 79 Just as with the dioxygenase enzymes, we do not know how similar the mechanisms of the different metal-containing monooxygenase enzymes are to one another. The enzyme for which we have the most information is cytochrome P-450, and we will therefore focus our discussion on that system. Speculations about the mechanisms for the other systems are discussed at the end of this section.