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Rover Eye
Rover Eye
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Alpha-2 macroglobulin is a plasma protein which acts as an anti-protease. It does so by a "bait mechanism" - the protease cleaves the bait domain, following which a conformational change causes binding of alpha2-macroglobulin with the protease, and consequent irreversible inhibition of the protease. 

This seems to be very similar to "suicide inhibition" or "mechanism based inhibition" - when an enzyme catalyses a substrate analog's conversion to an active inhibitor, which subsequently binds strongly to the enzyme to inactivate it. 

Is alpha2-macroglobulin's inhibition of proteases a case of suicide inhibition then? If it is, why is not more commonly described as that (I have not come across any description of alpha2-macroglobulin as a suicide inhibitor)?

Alpha-2 macroglobulin is a plasma protein which acts as an anti-protease. It does so by a "bait mechanism" - the protease cleaves the bait domain, following which a conformational change causes binding of alpha2-macroglobulin with the protease, and consequent irreversible inhibition of the protease. This seems to be very similar to "suicide inhibition" or "mechanism based inhibition" - when an enzyme catalyses a substrate analog's conversion to an active inhibitor, which subsequently binds strongly to the enzyme to inactivate it. Is alpha2-macroglobulin's inhibition of proteases a case of suicide inhibition then? If it is, why is not more commonly described as that (I have not come across any description of alpha2-macroglobulin as a suicide inhibitor)?

Alpha-2 macroglobulin is a plasma protein which acts as an anti-protease. It does so by a "bait mechanism" - the protease cleaves the bait domain, following which a conformational change causes binding of alpha2-macroglobulin with the protease, and consequent irreversible inhibition of the protease. 

This seems to be very similar to "suicide inhibition" or "mechanism based inhibition" - when an enzyme catalyses a substrate analog's conversion to an active inhibitor, which subsequently binds strongly to the enzyme to inactivate it. 

Is alpha2-macroglobulin's inhibition of proteases a case of suicide inhibition then? If it is, why is not more commonly described as that (I have not come across any description of alpha2-macroglobulin as a suicide inhibitor)?

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edit approved Sep 17, 2016 at 15:16
another 'Homo sapien'
edit approved Sep 17, 2016 at 15:16
another 'Homo sapien'
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Charles
Charles
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Enzyme Inhibition by alpha-2 macroglobulin

Alpha-2 macroglobulin is a plasma protein which acts as an anti-protease. It does so by a "bait mechanism" - the protease cleaves the bait domain, following which a conformational change causes binding of alpha2-macroglobulin with the protease, and consequent irreversible inhibition of the protease. This seems to be very similar to "suicide inhibition" or "mechanism based inhibition" - when an enzyme catalyses a substrate analog's conversion to an active inhibitor, which subsequently binds strongly to the enzyme to inactivate it. Is alpha2-macroglobulin's inhibition of proteases a case of suicide inhibition then? If it is, why is not more commonly described as that (I have not come across any description of alpha2-macroglobulin as a suicide inhibitor)?