Family

NADH:cytochrome b5 reductase (CBR) (IPR001834)

Short name: NADH-Cyt_B5_reductase

Overlapping homologous superfamilies

Family relationships

None.

Description

Flavoprotein pyridine nucleotide cytochrome reductases [PMID: 1748631] (FPNCR) catalyse the interchange of reducing equivalents between one-electron carriers and the two-electron-carrying nicotinamide dinucleotides. The enzymes include

  • ferredoxin:NADP+ reductases (FNR) [PMID: 8027025].
  • plant and fungal NAD(P)H:nitrate reductases [PMID: 1748631, PMID: 2204158].
  • NADH:cytochrome b5 reductases [PMID: 3654589].
  • 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 IPR001199), 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 [PMID: 3654589]. In the membrane-bound form, the N-terminal residue is myristoylated [PMID: 6436247]. Deficiency of the erythrocyte form causes hereditary methaemoglobinemia [PMID: 2695933].

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 (EC:1.7.1.1); an NAD(P)H-bispecific enzyme found in higher plants, algae and fungi (EC:1.7.1.2); and an NADPH-specific enzyme found only in fungi (EC:1.7.1.3) [PMID: 2204158]. 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 IPR001199); and the C-terminal portion of the protein is occupied by the FAD/NAD(P)H binding domain, which is similar to CBR [PMID: 2204158]. 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 [PMID: 7812715] and of Sus scrofa (Pig) NADH:cytochrome b5 reductase [PMID: 7893687] have been solved. The overall fold is similar to that of ferredoxin:NADP+ reductase [PMID: 8027025]: 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).

GO terms

Biological Process

GO:0055114 oxidation-reduction process

Molecular Function

GO:0016491 oxidoreductase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PRINTS