Ferritin-like superfamily of diiron-containing four-helix-bundle proteins; Ferritin-like, diiron-carboxylate proteins participate in a range of functions including iron regulation, mono-oxygenation, and reactive radical production. These proteins are characterized by the fact that they catalyze dioxygen-dependent oxidation-hydroxylation reactions within diiron centers; one exception is manganese catalase, which catalyzes peroxide-dependent oxidation-reduction within a dimanganese center. Diiron-carboxylate proteins are further characterized by the presence of duplicate metal ligands, glutamates and histidines (ExxH) and two additional glutamates within a four-helix bundle. Outside of these conserved residues there is little obvious homology. Members include bacterioferritin, ferritin, rubrerythrin, aromatic and alkene monooxygenase hydroxylases (AAMH), ribonucleotide reductase R2 (RNRR2), acyl-ACP-desaturases (Acyl_ACP_Desat), manganese (Mn) catalases, demethoxyubiquinone hydroxylases (DMQH), DNA protecting proteins (DPS), and ubiquinol oxidases (AOX), and the aerobic cyclase system, Fe-containing subunit (ACSF).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299831353   1 RHFWHQHQSMDTLVGVLSEYFAVERPWAYKDVWEEWVVDDFvGSYMSRLSPFGLKPPARLGDVARYVNDMHHSVAIALAA 80
Cdd:cd01057  246 KAFWRQHRLFDALVGMLMDYGTPKRVMSWKEFWEEWIEEDF-GSYFKDLEKYGLKKPWYWDDAKKEKDWYHHQLALGFYA 324

                         90       100
                 ....*....|....*....|....*..
gi 299831353  81 MWPLNFWRTDPMGPADYEWFENHYPGW 107
Cdd:cd01057  325 WWPTNFWRPDAPTPEEMEWFEEKYPGW 351

Aromatic and Alkene Monooxygenase Hydroxylase, subunit A, ferritin-like diiron-binding domain; Aromatic and Alkene Monooxygenase Hydroxylases, subunit A (AAMH_A). Subunit A of the soluble hydroxylase of multicomponent, aromatic and alkene monooxygenases are members of a superfamily of ferritin-like iron-storage proteins. AAMH exists as a hexamer (an alpha2-beta2-gamma2 homodimer) with each alpha-subunit housing one nonheme diiron center embedded in a four-helix bundle. The N-terminal domain of the alpha- and noncatalytic beta-subunits possess nearly identical folds, however, the beta-subunit lacks critical diiron ligands and a C-terminal domain found in the alpha-subunit. Methane monooxygenase is a multicomponent enzyme found in methanotrophic bacteria that catalyzes the hydroxylation of methane and higher alkenes (as large as octane). Phenol monooxygenase, found in a diverse group of bacteria, catalyses the hydroxylation of phenol, chloro- and methyl-phenol and naphthol. Both enzyme systems consist of three components: the hydroxylase, a coupling protein and a reductase. In the MMO hydroxylase, dioxygen and substrate interact with the diiron center in a hydrophobic cavity at the active site. The reductase component and protein coupling factor provide electrons from NADH for reducing the oxidized binuclear iron-oxo cluster to its reduced form. Reaction with dioxygen produces a peroxy-bridged complex and dehydration leads to the formation of complex Q, which is thought to be the oxygenating species that carries out the insertion of an oxygen atom into a C-H bond of the substrate. The toluene monooxygenase systems, toluene 2-, 3-, and 4-monooxygenase, are similar to MMO but with an additional component, a Rieske-type ferredoxin. The alkene monooxygenase from Xanthobacter strain Py2 is closely related to aromatic monooxygenases and catalyzes aromatic monohydroxylation of benzene, toluene, and phenol. Alkane omega-hydroxylase (AlkB) and xylene monooxygenase are members of a distinct class of integral membrane diiron proteins and are not included in this CD.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299831353   1 RHFWHQHQSMDTLVGVLSEYFAVERPWAYKDVWEEWVVDDFvGSYMSRLSPFGLKPPARLGDVARYVNDMHHSVAIALAA 80
Cdd:cd01057  246 KAFWRQHRLFDALVGMLMDYGTPKRVMSWKEFWEEWIEEDF-GSYFKDLEKYGLKKPWYWDDAKKEKDWYHHQLALGFYA 324

                         90       100
                 ....*....|....*....|....*..
gi 299831353  81 MWPLNFWRTDPMGPADYEWFENHYPGW 107
Cdd:cd01057  325 WWPTNFWRPDAPTPEEMEWFEEKYPGW 351

Aromatic and Alkene Monooxygenase Hydroxylase, subunit A, ferritin-like diiron-binding domain; Aromatic and Alkene Monooxygenase Hydroxylases, subunit A (AAMH_A). Subunit A of the soluble hydroxylase of multicomponent, aromatic and alkene monooxygenases are members of a superfamily of ferritin-like iron-storage proteins. AAMH exists as a hexamer (an alpha2-beta2-gamma2 homodimer) with each alpha-subunit housing one nonheme diiron center embedded in a four-helix bundle. The N-terminal domain of the alpha- and noncatalytic beta-subunits possess nearly identical folds, however, the beta-subunit lacks critical diiron ligands and a C-terminal domain found in the alpha-subunit. Methane monooxygenase is a multicomponent enzyme found in methanotrophic bacteria that catalyzes the hydroxylation of methane and higher alkenes (as large as octane). Phenol monooxygenase, found in a diverse group of bacteria, catalyses the hydroxylation of phenol, chloro- and methyl-phenol and naphthol. Both enzyme systems consist of three components: the hydroxylase, a coupling protein and a reductase. In the MMO hydroxylase, dioxygen and substrate interact with the diiron center in a hydrophobic cavity at the active site. The reductase component and protein coupling factor provide electrons from NADH for reducing the oxidized binuclear iron-oxo cluster to its reduced form. Reaction with dioxygen produces a peroxy-bridged complex and dehydration leads to the formation of complex Q, which is thought to be the oxygenating species that carries out the insertion of an oxygen atom into a C-H bond of the substrate. The toluene monooxygenase systems, toluene 2-, 3-, and 4-monooxygenase, are similar to MMO but with an additional component, a Rieske-type ferredoxin. The alkene monooxygenase from Xanthobacter strain Py2 is closely related to aromatic monooxygenases and catalyzes aromatic monohydroxylation of benzene, toluene, and phenol. Alkane omega-hydroxylase (AlkB) and xylene monooxygenase are members of a distinct class of integral membrane diiron proteins and are not included in this CD.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 299831353   1 RHFWHQHQSMDTLVGVLSEYFAVERPWAYKDVWEEWVVDDFvGSYMSRLSPFGLKPPARLGDVARYVNDMHHSVAIALAA 80
Cdd:cd01057  246 KAFWRQHRLFDALVGMLMDYGTPKRVMSWKEFWEEWIEEDF-GSYFKDLEKYGLKKPWYWDDAKKEKDWYHHQLALGFYA 324

                         90       100
                 ....*....|....*....|....*..
gi 299831353  81 MWPLNFWRTDPMGPADYEWFENHYPGW 107
Cdd:cd01057  325 WWPTNFWRPDAPTPEEMEWFEEKYPGW 351