Heme-thiolate monooxygenase

This enzyme [EC 1.14.15.3], also known as alkane 1-monooxygenase, lauric acid ca-hydroxylase, fatty acid hydroxylate fatty acids in the [Pg.47]

This enzyme [EC 1.6.2.4] (also referred to as NADPH ferrihemoprotein reductase, NADPHxyto-chrome P450 reductase, TPNH2 cytochrome c reductase, and ferrihemoprotein P450 reductase) catalyzes the reaction of NADPH with two ferricytochrome to produce NADP+ and two ferrocytochrome. The protein requires FMN and FAD. In addition, it also catalyzes the reduction of heme-thiolate-dependent monooxygenases (e.g.,... 

This heme-thiolate-dependent enzyme [EC 1.14.15.4], also known as steroid 11/3-monooxygenase, catalyzes the reaction of a steroid with reduced adrenal ferredoxin and dioxygen to produce an 11/3-hydroxysteroid, oxidized adrenal ferredoxin, and water. The enzyme also catalyzes the hydroxylation of steroids at the 18-position and can catalyze the conversion of 18-hydroxycorticosterone into aldosterone. 

Another interesting group of oxidoreductases are the cytochromes P450 (Figure 19). Those heme-thiolate proteins act as monooxygenases and catalyze a wide range of oxidative reactions, such as hydroxylation and epoxidation... 

Oxidation (the introduction of another phenolic hydroxyl group) is effected by A -methylcoclaurine 3 -monooxygenase (EC 1.14.13.71), the gene for which (CYP80B1) produces a heme-thiolate cytochrome P4so-dependent monooxygenase protein that uses reduced NADPH as a cofactor and oxygen ( ) to produce water, oxidized cofactor (nicotinamide adenine dinucleotide [NADP ]), and (5)-3 -hydroxy-A-methylcoclaurine. 

Our laboratory is also studying the directed evolution of a new type of potentially ligninolytic peroxidase classified as unspecific peroxygenase, UPO (EG 1.11.2.1). UPO was initially defined as a heme-thiolate peroxidase, exhibiting both per-oxidative and peroxygenative activities toward aromatic compounds (aromatic peroxygenase, also referred to as APO [26, 75]). However, more recent studies have described the monooxygenase activity of UPO toward ahphatic compounds (UPO,... 

The monooxygenases [65-70] are characterized by the axial attachment of the heme cofactor to a thiolate functionality from a cysteine residue of the protein matrix. The binding pockets of monooxygenases are usually organized in such a way as to lead the substrate directly to the active FeO subunit of the porphyrin. This... 

The resting state, the low-spin Fe complexes of the family of monooxygenase and oxidase enzymes known as the cytochromes P450 see Iron Heme Proteins, Mono- Dioxygenases), have one cysteine thiolate as the proximal ligand T258 water molecule as the distal... 

Cytochrome P-450, which is the most extensively studied of the monooxygenase proteins, has a heme-iron active center with an axial thiol ligand (a cysteine residue). However, most chemical model investigations use simple iron(III) porphyrins without thiolate ligands. As a result, model mechanisms for cytochrome P-450 invoke a reactive intermediate that is formulated to be equivalent to Compound I of horseradish peroxidase, (por+-)Fe =0, with a high-potential porphyrin cation radical. Such a species would be reduced by thiolate, and therefore is an unreasonable formulation for the reactive center of cytochrome P-450. 

In fungi, a somewhat different type of NOR activity occurs, at a single heme center, where the proximal axial ligand to the iron is a cysteine thiolate, rendering the system similar to the P450 monooxygenase active-site structure [154] ... 

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