Nitric Oxide Synthase: Difference between revisions

The reductase domain is, as mentioned, bound to the oxygenase domain by a linker region that binds [http://en.wikipedia.org/wiki/Calmodulin calmodulin].  The calmodulin linker consists of 32 residues. The binding of Ca²⁺ loaded calmodulin to the linker region is found to be crucial in that it induces a conformational change which is essential for electron transfer. The NOS activity is thereby dependent upon the Ca²⁺ concentration It is important to emphasize that the electron transfer occurs from the reductase domain of one subunit to the oxygenase domain of the opposite subunit (i.e. a trans transfer).  The conformational change induced by calmodulin binding brings the mentioned reductase and oxygenase  domains closer together, thus the linker acts as a hinge. The electron transfer occurs two times per  NO molecule produced. The first transfer supplies an electron for the conversion of L-arginine to its intermediate, the second transfer for the conversion of the intermediate Citrulline and NO. In general the reductase domain can be divided into three subdomains: the NADPH binding domain, the FAD binding domain, and the FMN binding domain. The NADPH and FAD binding domains are associated whereas the FAD and FMN domains are connected by an α-helical binding domain. The electrons donated by NADPH is passed on to FAD. FAD then shuttles the electron to FMN. The FMN binding domain is a flexible domain and here the conformational change occurs. The binding of calmodulin rotates the reductase domain and oxygenase domain along a vertical axis, thus bringing the reductase domain closer to the opposite oxygenase domain. The electron can then due to shorter distance be passed on the the heme group of the oxygenase domain <ref>PMID: 15208315</ref>. The iron ion in the heme group is reduces from iron (III) to iron (II) which catalyses the substrate reaction.

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