Friday, 11 May 2012

Salvestrol Activase Enzyme Crystallised

There are 3 important CYP enzymes in the human body responsible for salvestrol metabolism which are CYP1A1, CYP1A2, and CYP1B1. The first two are alpha salvestrol activases which hydroxlate the A-ring, whilst CYP1B1 is a beta salvestrol activase that uniquely hydroxylates the B-ring.

CYP1A2 is expressed in the liver that catalyses the first step of dietary salvestrol activation converting salvestrol T30 to salvestrol Q40, whereas CYP1B1 is expressed in the cancer cells and is responsible for the bioactivation of salvestrol Q40 to the ultimate anticancer metabolite M50. So the activation of salvestrols is a two-step process involving a first activation step in the liver followed by a second activation step within the tumour cells and the two enzymes are co-operating in this process.

The 3 dimensional structure of the enzyme CYP1A2 has finally been solved using X-ray crystal diffraction analysis. Note the complexity of the structure which reveals the marvelous design present in mother nature at the molecular level. There are 12 alpha helices all connected and folded up so as to form an inner cavity that selectively binds a salvestrol molecule in the correct orientation to be hydroxlated by the reactive haeme bound iron oxide at its centre. Two of the alpha helices loop back to form a hinged lid which opens and closes through the catalytic cycle and the whole enzyme performs as an esquisite molecular machine.

This enzyme has evolved over tens of millions of years to allow the human body to selectively bind and metabolise salvestrols, and this shows how important this process must be to human health by eliminating cancer cells from the body.

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