Nitric Oxide Synthase: Difference between revisions
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The NOS homodimer is composed of two subunits, each containing two domains: an oxygenase domain and a reductase domain. The subunits are held together by a Zinc ion, which is bound by 4 cystein amino | The NOS homodimer is composed of two subunits, each containing two domains: an oxygenase domain and a reductase domain. The subunits are held together by a Zinc ion, which is bound by 4 cystein amino acids present in the oxygenase domain, two in each domain. Further, many amino acid interactions also hold the sunbunits together. Binding of the two types of domains is caused by CaM. The reductase domain supplies electrons for the NOS reaction which takes place in the oxygenase domain. The reductase domain contains two redox-active prosthetic groups, FAD and FMN. NADPH binds to the domain and passes on an electron to FAD which passes the electron on to FMN. FMN passes the electron on to the Heme in the oxygenase domain of the opposite subunit. The oxygenase domain contains H<sub>4</sub>B (5,6,7,8-tetrahydrobiopterin)and the already mentioned Heme ion (Fe(III)). These two are also redox active groups. H<sub>4</sub>B is required by NOS in order to produce NO and not H<sub>2</sub>O<sub>2</sub>. Besides Heme and H<sub>4</sub>B, the oxygenase domain binds the substrate L-arginine which takes part in the NO synthase reaction (see below). | ||
In mammals three isozymes of NOS has been identified: Neuronal NOS [[(nNOS)]], inducible NOS [[(iNOS)]], and endothelial NOS [[(eNOS)]]. One differentiates between constitutive NOS (always produced - eNOS and nNOS) and inducable NOS (iNOS). Constitutive NOS are regulated by calcium binding to the CaM region and is thus regulated by calcium. nNOS produces NO in nervous tissue in both the peripheral and the central nervous system. nNOS functions in cell signaling and communication - a vital part of the nervous tissue. eNOS controls the amount of NO signaling in the endothelial cells (eg. blood vessel dilation). iNOS is induced to produce NO only when needed. For example when the immune system is activated. iNos is not regulated by calcium. The NOS enzymes is found in numeral organisms. Most facts used at this page are taken from the human NOS. The active site and different binding regions are highly conserved and therefore sites from other organisms will be used as well. | In mammals three isozymes of NOS has been identified: Neuronal NOS [[(nNOS)]], inducible NOS [[(iNOS)]], and endothelial NOS [[(eNOS)]]. One differentiates between constitutive NOS (always produced - eNOS and nNOS) and inducable NOS (iNOS). Constitutive NOS are regulated by calcium binding to the CaM region and is thus regulated by calcium. nNOS produces NO in nervous tissue in both the peripheral and the central nervous system. nNOS functions in cell signaling and communication - a vital part of the nervous tissue. eNOS controls the amount of NO signaling in the endothelial cells (eg. blood vessel dilation). iNOS is induced to produce NO only when needed. For example when the immune system is activated. iNos is not regulated by calcium. The NOS enzymes is found in numeral organisms. Most facts used at this page are taken from the human NOS. The active site and different binding regions are highly conserved and therefore sites from other organisms will be used as well. | ||