transition state inhibitor question

[theonlytycrane]

An enzyme + substrate interact and progress through a transition state as part of a reaction. I previously thought of transition state inhibitors as substrate-like molecules that interact with an enzyme, but get it "stuck" in the transition state such that the reaction does not go to completion while other substrate molecules are blocked from reacting with the enzyme.

To me, the given answer sounds like the inhibitor is binding to the transition state structure directly. Am I misinterpreting this answer choice?

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[aldol16]

An enzyme + substrate interact and progress through a transition state as part of a reaction. I previously thought of transition state inhibitors as substrate-like molecules that interact with an enzyme, but get it "stuck" in the transition state such that the reaction does not go to completion while other substrate molecules are blocked from reacting with the enzyme.

There are two different kinds of inhibitors you can have. You can have substrates that do some chemistry and then get stuck - think sarin - or substrates that bind to the transition state and get stuck. In the latter case, the substrate binds to the active site with some affinity and then to the transition state with a greater affinity. That inhibits the active site.

 

[FutureD0C17]

Suicide inhibitors bind the active site, partially react, and then get stuck. I always remember this by thinking "suicide bomber". A kamikaze type mission.

Transition state inhibitors mimic the conformation of the transition state and bind with a greater affinity.

I don't understand the question though, how are we supposed to know which substrate binds more effectively to neuraminidase?

 

[aldol16]

I don't understand the question though, how are we supposed to know which substrate binds more effectively to neuraminidase?

This is a KA question and so I think the Kd values were given in the passage.

 

[theonlytycrane]

It's a KA question and actually no kd values were given The passage states that Oseltamivir acts as an inhibitor, but leaves out enough information to accurately determine the relative affinities for the enzyme.

 

[aldol16]

It's a KA question and actually no kd values were given The passage states that Oseltamivir acts as an inhibitor, but leaves out enough information to accurately determine the relative affinities for the enzyme.

Ah I see. I went back and looked at the question. You know that the inhibitor must bind more strongly because otherwise it wouldn't be an inhibitor at all. If it binds to the TS less strongly than the substrate, then the substrate would outcompete it and adding the inhibitor would be like adding no inhibitor. This question hinges on the fact that the passage tells you it's a drug that is a competitive inhibitor of the enzyme.