Electron transfer nitric oxide synthase flavins

E. Roles for Nitric Oxide Synthase Flavins in Electron Transfer... 

Siddhanta U., Presta, A., Fan, B., Wolan, D., Rousseau, D. L., Stuehr, D.)., Domain swapping in inducible nitric-oxide synthase. Electron transfer occurs between flavin and heme groups located on adjacent subunits in the dimmer, J. Biol. Chem. 273 (1998), p. 18950-18958... 

Figure 11.4. Reaction catalyzedby Nitric oxide synthase (a), and arrangement of the coenzymes in the dimer (b). Electrons flow from NADPH and flavins of one snbnnit to the heme of the other. Arg denotes the snbstrate binding site. Tetrahydrobiopterin (BH4) also participates in electron transfer.

FIGURE I Role for calmodulin (CaM) in triggering interdomain electron transfer to the nitric oxide synthase (NOS) heme iron. Electrons derived from NADPH can transfer only into the flavin centers of CaM-free neuronal NOS (A). CaM binding to NOS occurs in response to elevated Ca concentrations, and this enables electrons to transfer from the flavins to the heme iron. Heme iron reduction is associated with increased NADPH oxidation and results in (B) superoxide (O2) production in the absence of L-arginine or (C) nitric oxide (NO) synthesis in the presence of L-arginine. FAD, Flavin-adenine dinucleotide FMN, flavin mononucleotide. 

FIGURE 2 Proposed dual mode for calmodulin (CaM) control of nitric oxide synthase (NOS) electron transfer. Neuronal NOS is composed of a reductase and an oxygenase domain, shown as two circles. CaM binding to NOS activates at two points in the electron transfer sequence (1) It increases the rate at which NADPH-derived electrons are transferred into the flavins, and (2) it enables the flavins to pass electrons to the oxygenase domain of NOS. Activation at the first point is associated with an increase in reductase domain-specific catalytic activities, such as electron transfer to cytochrome c or ferricyanide (FeCN ). Activation at the second point is associated with a reduction of NOS heme iron, an initiation of NO synthesis from L-arginine (Arg), or a reduction of Oj to form superoxide (O2) in the absence of substrate. FAD, Flavin-adenine dinucleotide FMN, flavin mononucleotide NO, nitric oxide. 

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