Sandbox 5
| This sandbox will be used for a student project at University of Copenhagen from April until the 1st of July 2009. Please don't edit the page until then. |
Nitric Oxide Synthase - NOSNitric Oxide Synthase - NOS
Nitric Oxide Synthase (NOS) is a group of enzymes catalysing L-arginine to yield L-Citrulline and Nitric Oxide[1] (NO). NOS is a homodimeric protein with 125- to 160-kD subunits. An overview of the NOS homodimer is given below. All cofactors are included and the electron transfer pathway which takes place in NOS is indicated.
The NOS homodimer is composed of two types of domains: an oxygenase domain and a reductase domain. Each subunit is held together by a Zinc ion, which is bound by the amino acid Cystein present in the oxygenase. Binding of the 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 is a Flavin mononucleotide. FMN passes the electron on to the Heme in the oxygenase domain on the opposite subunit. The oxygenase domain contains BH4 (5,6,7,8-tetrahydrobiopterin)and the already mentioned Heme ion (Fe(III)). These two are also redox active groups. BH4 is required by NOS in order to produce NO and not H2O2. Besides Heme and BH4, 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). (~The NOS enzymes is found in numeral organisms. Most facts used here is from the human NOS, but sites from different organisms are used.~). Neuronal NOS is producing NO in the nervous tissue in both the peripheral and the central nervous system. nNOS is functioning in cell signaling and communication - a vital part of the nervous tissue. Inducible NOS is connected with the immune system or in general...(!?). Endothelial NOS is controlling the amount of NO signaling in the endothelial cells eg. blood vessel dilation.
The NOS reaction requires five redox-active cofactors.
Substrate bindingSubstrate binding
The active site is highly conserved in the different NOS species. Thus it is possible to discuss substrate binding i general terms. The NOS enzyme binds its substrate by hydrogen bindings both to the guanidino[2] end and the amino acid end (EVT FIG!).
|
binds its substrate (L-arginine) by coordinating CO to the heme at the site occupied by oxygen....[1].
The reaction of NOS:The reaction of NOS:
As previously described NOS is an enzyme split in to different domains; the N-terminal oxygenase domain and the C-terminal reductase domain.
The oxygenase domain is where the production of NO takes place, whereas the reductase domain provides the electrons necessary to drive the reaction in the oxygenase domain. The reaction is:
INDSÆT FIGUR
The amino acid L-Arginine is turned in to L-Citrulline and NO. The reaction is driven by the oxidation of NADPH to NADP+, which in total yields 5 electrons for the reaction. The reaction above therefore takes both the oxygenase and the reductase domain into account.
StructureStructure
NOS is a homodimeric protein with 125- to 160-kD subunits. An overview of the NOS homodimer is given below. All cofactors are included and the electron transfer pathway which takes place in NOS is indicated.
The NOS homodimer is composed of two types of domains: a oxygenase domain and a reductase domain. Each subunit is held together by a Zinc ion, which is bound by the amino acid Cystein present in the oxygenase. Binding of the 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 prothetic groups, FAD and FMN. NADPH binds to the domain and passes on an electron to FAD which passes the electron on to FMN. FMN is a Flavin mononucleotide. FMN passes the electron on to the Heme in the oxygenase domain on the opposite subunit. The oxygenase domain contains BH4 (5,6,7,8-tetrahydrobiopterin)and the already mentioned Heme ion (Fe(III)). These two are also redox active groups.BH4 is required by NOS in order to produce NO and not H2O2. Besides Heme and BH4, the oxygenase domain binds the substrate L-arginine which takes part in the NO synthase reaction (see below).
This is a placeholderThis is a placeholder
This is a placeholder text to help you get started in placing a Jmol applet on your page. At any time, click "Show Preview" at the bottom of this page to see how it goes.
Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load and display another structure.
This is a placeholder - MetteThis is a placeholder - Mette
This is a placeholder text to help you get started in placing a Jmol applet on your page. At any time, click "Show Preview" at the bottom of this page to see how it goes.
Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load and display another structure.
This is a placeholder MathildeThis is a placeholder Mathilde
This is a placeholder text to help you get started in placing a Jmol applet on your page. At any time, click "Show Preview" at the bottom of this page to see how it goes.
Replace the PDB id (use lowercase!) after the STRUCTURE_ and after PDB= to load and display another structure.