Peptidylglycine a-hydroxylating monooxygenase

PHM peptidylglycine a-hydroxylating monooxygenase RVM rostral ventromedial medulla... 

Figure 14.3 The reaction catalysed by peptidylglycine a-hydroxylating monooxygenase.

Figure 14.4 The dioxygen site in peptidylglycine a-hydroxylating monooxygenase incubated in the presence of IYT. (From Bento et al., 2006. With kind permission of Springer Science and Business Media.)...

Klinman JP. The copper-enzyme family of dopamine 3-mono-oxygenase and peptidylglycine a-hydroxylating monooxygenase resolving the chemical pathway for substrate hydroxylation. J. Biol. Chem. 2006 281 3013-3016. 

Chen P, Solomon El. Oxygen activation by the noncoupled binu-clear copper site in peptidylglycine a-hydroxylating monooxygenase. Reaction mechanism and role of the noncoupled nature of the active site. J. Am. Chem. Soc. 2004 126 4991-5000. 

Finally, many enzymes are kinetically complex, and have multiple steps that partially limit both k at and k t/KM. One approach is to use single-turnover studies to obtain the rate of the chemical step and the kinetic isotope effects by this noncompetitive technique. Several examples of single-turnover studies of enzymes that exhibit the characteristic of turmeling are in the literature [11, 12]. Alternatively, tools that allow microscopic rate constants to be calculated from observed rate constants can be applied. This approach has been documented for peptidylglycine-a-hydroxylating monooxygenase [13], and more recently, for dihydrofolate reductase [14]. 

Peptidylamidoglycolate lyase completes the peptide ami-dation process initiated by peptidylglycine a-hydroxylating monooxygenase vide supra. Section 2.1.3). This zinc-dependent function converts the hydroxyglycine containing peptide to the amidated form and releases glyoxalate (equation 8) ... 

The non-coupled binuclear copper enzymes include dopamine p-monooxy-genase (DpM) and peptidylglycine a-hydroxylating monooxygenase (PHM). Both enzymes catalyze substrate C-H bond hydroxylation (at a Gly backbone C-H bond in PHM and a dopamine benzylic C-H bond in DpM), and kinetic and mechanistic studies have shown that the reaction mechanisms for both DpM and PHM are very similar [14]. The active site structure from the crystal structures of PHM indicates... 

Prigge ST, Kolhekar AS, Eipper BA, Mains RE, Amzel LM. 1997. Amidation of bioactive peptides the structure of peptidylglycine a-hydroxylating monooxygenase. Science 278 1300-1305. 

Bell J, El Meskini R, DAmato D, Mains RE, Eipper BA. 2003. Mechanistic investigation of peptidylglycine a-hydroxylating monooxygenase via intrinsic tryptophan fluorescence and mutagenesis. Biochemistry 42 7133-7142. 

Eipper BA, Quon ASW, Mains RE, Boswell JS, Blackburn NJ. 1995. The catalytic core of peptidylglycine a-hydroxylating monooxygenase investigation by site-directed mutagenesis, Cu x-ray absorption spectroscopy, and electron paramagnetic resonance. Biochemistry 34 2857-2865. 

Chen P, Bell J, Eipper BA, Solomon El. 2004. Oxygen activation by the noncoupled binuclear copper site in peptidylglycine a-hydroxylating monooxygenase spectroscopic definition of the resting sites and the putative Cum(II)-OOH intermediate. Biochemistry 43 5735—5747. 

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