The Molecular History of Eukaryotic Life  Nitric Oxide Synthase 


David Nelson  Dec. 13, 2000

	Nitric oxide synthase produces NO radical and citrulline from arginine. The NO is 
a signal that rapidly degrades and it cannot be turned off.  It also diffuses through 
membranes so that no transport mechanism is needed.  Its action is short lived and 
localized.  The C-terminal of the enzyme NOS has 36% sequence identity to cytochrome 
P450 reductase.  It contains FMN, FAD and a binding site for NADPH.  This part of the 
molecule must have evolved from cytochrome P450 reductase.  The N-terminal has the 
heme and the active site where the NO is made.  There is a heme thiolate  (S-) ligand 
which gives the spectral properties of a cytochrome P450 enzyme, but other highly 
conserved features seen in all P450s are missing.  This part of the enzyme is probably 
not derived from a P450 ancestor, but arose from some other source.  The thiolate anion 
ligand to the heme seems to be a case of convergent evolution.  The whole protein must be 
the result of gene fusion between the P450 reductase part and some other gene that coded 
for the N-terminal half.  There are a few reports of NOS activity in insects, plants and 
yeast, but the genes for these activities are not identified yet.

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