Site-binding, phosphate-amide

The observable properties of a polyelectrolyte depend upon the distribution of small ions in its neighborhood. This distribution is affected by two types of "binding" (20, 21). The first involves the binding of counterions to specific sites of the macroion, i.e., "site-binding" (20). The second involves the binding of counterions anywhere in the vicinity of the macroion, i.e., "ionic-atmosphere-binding". The site-binding of phosphates to nonpolar amides is unique. 

The interpretation offered here depends on the feasibility of phosphate-amide group binding. In the discussion section below, evidence is presented concerning both this feasibility and also concerning the unique nature of this form of site binding. 

In 1989, BH4 was found to be a cofactor for nitric oxide synthase (NOS) [ 126, 127]. BH4 is also involved in dimerization of NOS, as NOS is catalytically active in a homodimer structure. Three isoforms of NOS exist neuronal NOS (NOS 1), inducible NOS (NOS 2) and endothelial NOS (NOS 3). BH4 is essential for all NOS isoforms. The NOS isoforms share approximately 50-60% sequence homology. Each NOS polypeptide is comprised of oxygenase and reductase domains. An N-terminal oxygenase domain contains iron protoporphyrin IX (heme), BH4 and an arginine binding site, and a C-terminal reductase domain contains flavin mononucleotide (FMN), and a reduced nicotin-amide adenine dinucleotide phosphate (NADPH) binding site. 

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