Nitric oxide dioxygenase
| nitric oxide dioxygenase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 E. coli flavohemoglobin/NOD structure (PDB 1gvh). green = reductase domain, blue = hemoglobin domain | |||||||||
| Identifiers | |||||||||
| EC no. | 1.14.12.17 | ||||||||
| CAS no. | 214466-78-1 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
A nitric oxide dioxygenase (EC 1.14.12.17) is an enzyme that catalyzes the chemical reaction
- NO + O2 + NAD(P)H NO3- + NAD(P)+ + H+
The 3 substrates of this enzyme are nitric oxide, O2, NADH, (or NADPH), whereas its 3 products are nitrate, NAD+, (or NADP+), and H+. NO dioxygenase belongs to the family of oxidoreductases, more specifically those acting on paired donors, with O2 as oxidant and with incorporation of two atoms of oxygen into the other donor.
NODs serve two important physiological functions in diverse life forms. They prevent NO toxicity and regulate NO signalling. NODs belong to the larger family of well-established free radical and reactive oxygen detoxifying enxymes that includes superoxide dismutase, catalase, and peroxidase.
Discovery
Nitric oxide dioxygenase was discovered, and first reported in 1998, by Gardner's group as an inducible O2-dependent protective enzymatic activity[1] associated with the Escherichia coli flavohemoglobin.[2]
Structure
The flavohemoglobin protein contains two domains: a NAD(P)H-binding flavin adenine nucleotide (FAD) "reductase" domain and a b-type heme-containing "hemoglobin" domain. The reductase domain supplies an electron to the heme iron to achieve a high rate of catalytic NO dioxygenation.
Function
In addition to the flavohemoglobins, many members of the hemoglobin superfamily including the muscle myoglobin, the non-symbiotic plant hemoglobin and symbiotic plant leghemoglobin, the neuronal neuroglobin, and the mammalian cytoplasmic cytoglobin [3] [4] appear to function as nitric oxide dioxygenases (NODs), although the cellular electron donor(s) for many globins have yet to be defined. Electron donors may include ascorbate, cytochrome b5 or ferredoxin reductase.[5] The catalytic NO dioxygenation can be written in its simplest form:
- NO + O2 + e- NO3-
NODs, as well as many hemoglobins that function as NODs, are distributed to most life forms including bacteria, fungi, protists, worms, plants and animals. In fact, nitric oxide dioxygenation appears to be a primal function for members of the hemoglobin superfamily. Moreover, it is becoming increasingly evident that the NOD function of globins is much more common than the paradigmatic O2 transport-storage function.[6] Other proteins that may act as NODs include mammalian microsomal cytochrome P450(s)[7] and a novel O2-binding cytochrome b from Rhodobacter sphaeroides.[8]
References
- ^ Gardner PR, Costantino G, Salzman AL (1998). "Constitutive and adaptive detoxification of nitric oxide in Escherichia coli. Role of nitric-oxide dioxygenase in the protection of aconitase". J. Biol. Chem. 273 (41): 26528–33. doi:10.1074/jbc.273.41.26528. PMID 9756889.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Gardner PR, Gardner AM, Martin LA, Salzman AL (1998). "Nitric oxide dioxygenase: an enzymic function for flavohemoglobin". Proc. Natl. Acad. Sci. U. S. A. 95 (18): 10378–83. doi:10.1073/pnas.95.18.10378. PMC 27902. PMID 9724711.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Gardner AM, Cook MR, Gardner PR (2010). "Nitric-oxide dioxygenase function of human cytoglobin with cellular reductants and in rat hepatocytes". J. Biol. Chem. 285 (31): 23850–57. doi:10.1074/jbc.M110.132340. PMID 20511233.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Halligan KE, Jourd'heuil FL, Jourd'heuil D (2009). "Cytoglobin is expressed in the vasculature and regulates cell respiration and proliferation via nitric oxide dioxygenation". J. Biol. Chem. 284 (13): 8539–47. doi:10.1074/jbc.M808231200. PMID 19147491.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Gardner PR (2005). "Nitric oxide dioxygenase function and mechanism of flavohemoglobin, hemoglobin, myoglobin and their associated reductases". J. Inorg. Biochem. 99 (1): 247–66. doi:10.1016/j.jinorgbio.2004.10.003. PMID 15598505.
- ^ Vinogradov SN, Moens L (2008). "Diversity of globin function: Enzymatic, transport, storage and sensing". J. Biol. Chem. 283 (14): 8773–77. doi:10.1074/jbc.R700029200. PMID 18211906.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Hallstrom CK, Gardner AM, Gardner PR (2004). "Nitric oxide metabolism in mammalian cells: Substrate and inhibitor profiles of a NADPH-cytochrome P450 oxidoreductase-coupled microsomal nitric oxide dioxygenase". Free Radical Biol. Med. 37 (2): 216–28. doi:10.1016/j.freeradbiomed.2004.04.031. PMID 15203193.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Li BR, Ross Anderson JL, Mowat CG, Miles CS, Reid GA, Chapman SK (2008). "Rhodobacter spaeroides haem protein: a novel cytochrome with nitric oxide dioxygenase activity". Biochem. Soc. Trans. 36: 992–93. doi:10.1042/BST0360992. PMID 18793176.
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