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Finding nitric oxide in an oxygen haystack: Marletta

Soluble guanylate cyclase, an enzyme that senses nitric oxide

A glimpse of how molecular processes such as muscle relaxation and neuronal signaling are triggered by nitric oxide is published in the June issue of Nature Chemical Biology. Michael Marletta and colleagues show how nitric oxide acts as a signaling molecule in the presence of vast excesses of oxygen - until now scientists had puzzled as to how this occurs.

Although the nitric oxide-sensing enzyme, soluble guanylate cyclase (sGC), is well characterized, the basis for selective binding of nitric oxide was not known. However, by changing a single amino acid in the active site of the enzyme from isoleucine to tyrosine, the authors converted sGC from an enzyme that excludes oxygen to one that binds oxygen. Conversely, a related bacterial enzyme with a tyrosine in the active site normally binds oxygen, but the oxygen affinity can be dramatically reduced by removal of the tyrosine. These results suggest that the active site of sGC is designed to prevent oxygen binding by maintaining a hydrophobic pocket with no hydrogen-bond donor to stabilize bound oxygen.

The authors hypothesize that this simple mechanism for controlling oxygen binding has allowed members of this enzyme family to evolve as both oxygen and nitric oxide sensors.

Related sites:

Michael Marletta's website

Nature Chemical Biology website

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