Nitric Oxide Synthase: Difference between revisions

The reductase domain of the NOS homodimer will not be discussed thoroughly at this page. However, a short discussion of the electron transfer which occurs will be given along with an introduction to the bound cofactors and the general structure.  

The reductase domain is, as mentioned, bound to an oxygenase domain by a calmodulin linker. This linker responds to Ca²⁺ -ions (constitutive NOS isoforms).  The calmodulin linker consists of 32 residues and contains a binding region for the Ca²⁺ -ions. This binding is found to be crucial in that it induces a conformational change which is essential for electron transfer. 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 Ca²⁺ -ions 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 Citruline and NO. In general the reductase domain can be divided into three binding domains: 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. An electron is donated by NADPH, which passes the electron on to FAD. FAD shuttles on the electron to FMN. The FMN binding domain is a flexible domain and here the conformational change occurs. The Calmodulin linker 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 bound by the oxygenase domain <ref>PMID: 15208315</ref>.