Peptidylglycine a-hydroxylating monoxygenase

Chen, P. and Solomon, E.I. (2004). Oxygen activation by the noncoupled binuclear copper site in peptidylglycine-a-hydroxylating monoxygenase. Reaction mechanism and role of the noncoupled nature of the active site. J. Am. Chem. Soc. 126, 4991-5000... 

Peptidyl-a-hydroxylating monoxygenase, 67-68 Peptidylglycine a-hydroxylating monoxygenase, A9t... 

Somewhat related to the chemistry observed with the peptidylglycine-a-hydroxylating monoxygenase (PHM), the aerobic oxidation of cyclohexane has been studied by several groups. Murahashi et al. have reported that with CuCl2 and acetaldehyde and in the presence of 18-crown-6, cyclohexanone was obtained as the major product (cyclohexanol was formed as the major by-product) under relativelymild conditions (70 °C) [109,110]. Turnover numbers of up to 1600 were achieved with 61% yield of cyclohexanone at 1 atm of O2, but the precise mechanism has not been elucidated (Eq. 7). 

Tyrosinase is both an oxidase and a hydroxylase. Some other copper enzymes have only a hydroxylase function. One of the best understood of these is the peptidylglycine a-hydroxylating monoxygenase, which catalyzes the first step of the reaction of Eq. 10-11. The enzyme is a colorless two-copper protein but the copper atoms are 1.1 nm apart and do not form a binuclear center.570 Ascorbate is an essential cosubstrate, with two molecules being oxidized to the semidehydro-ascorbate radical as both coppers are reduced to Cu(I). A ternary complex of reduced enzyme, peptide, and 02 is formed and reacts to give the hydroxylated product.570 A related two-copper enzyme is dopamine (J-monooxygenase, which utilizes 02 and ascorbate to hydroxylate dopamine to noradrenaline (Chapter 25).571/572 These and other types of hydroxylases are compared in Chapter 18. 

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