We propose to solve the three-dimensional x-ray structure of bovine eNOS (endothelial nitric oxide synthase) alone and complexed with calmodulin. eNos plays important roles in antithrombosis and anti-atherosclerosis. By determining the structure of eNOS we hope to facilitate structure-base design drugs that activate or inhibit the enzyme. We plan to address a series of mechanistic and structural questions such as: How is the activity of eNOS regulated by cofactors such as calmodulin? Why does NO (nitric oxide) not irreversibly deactivate the heme moiety? How is the structure of eNOS related to that of cytochrome P-450 reductase, which has a homologous amino acid sequence?
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