| Type: | Family | Name: | NADH:cytochrome b5 reductase (CBR) |
| Description: | Flavoprotein pyridine nucleotide cytochrome reductases [] (FPNCR) catalyse the interchange of reducing equivalents between one-electron carriers and the two-electron-carrying nicotinamide dinucleotides. The enzymes includeferredoxin:NADP+reductases (FNR) [].plant and fungal NAD(P)H:nitrate reductases [, ].NADH:cytochrome b5 reductases [].NADPH:P450 reductases.NADPH:sulphite reductases.nitric oxide synthases.phthalate dioxygenase reductase.and various other flavoproteins.NADH:cytochrome b5 reductase (CBR) serves as electron donor for cytochrome b5, a ubiquitous electron carrier (see ), thus participating in a variety of metabolic pathways (including steroid biosynthesis, desaturation and elongation of fatty acids, P450-dependent reactions, methaemoglobin reduction, etc.). A membrane-bound form of CBR is located on the cytosolic side of the endoplasmic reticulum, while a soluble form is found in erythrocytes []. In the membrane-bound form, the N-terminal residue is myristoylated []. Deficiency of the erythrocyte form causes hereditary methaemoglobinemia [].In biological nitrate assimilation, reduction of nitrate to nitrite is catalysed by the multidomain redox enzyme NAD(P)H:nitrate reductase (NR). Three forms of NR are known: an NADH-specific enzyme found in higher plants and algae (); an NAD(P)H-bispecific enzyme found in higher plants, algae and fungi (); and an NADPH-specific enzyme found only in fungi () []. NR can be divided into 3 structure/function domains: the molybdopterin cofactor binds in the N-terminal domain; the central region is the cytochrome b domain, which is similar to animal cytochrome b5 (see ); and the C-terminal portion of the protein is occupied by the FAD/NAD(P)H binding domain, which is similar to CBR []. The catalytic reduction of nitrate to nitrite can be viewed as a single polypeptide electron transport chain with electron flow from NAD(P)H ->FAD ->cytochrome b5 ->molybdopterin ->NO(3). Thus, the flavin domain of NR is functionally identical to CBR.To date, the 3D-structures of the flavoprotein domain of Zea mays(Maize) nitrate reductase [] and of Sus scrofa(Pig) NADH:cytochrome b5 reductase [] have been solved. The overall fold is similar to that of ferredoxin:NADP+reductase []: the FAD-binding domain (N-terminal) has the topology of an anti-parallel beta-barrel, while the NAD(P)-binding domain (C-terminal) has the topology of a classical pyridine dinucleotide-binding fold (i.e. a central parallel beta-sheet flanked by 2 helices on each side). | Short Name: | NADH-Cyt_B5_reductase |
