August 15, 2022, 08:35:12 PM
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Topic: Carboxylate attack Histidine Proton  (Read 350 times)

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Offline helplessnerd0402

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Carboxylate attack Histidine Proton
« on: September 24, 2021, 10:32:01 AM »
I'm working on an enzyme mechanism where I start with a histidine at a net charge of zero. In the first step, histidine takes a proton from water (giving histidine a +1 charge). At the end of the reaction, histidine is still protonated and one of my products is a carboxylate. Would the carboxylate attack histidine's proton, giving me a carboxylic acid and a deprotonated histidine? The pKa for my carboxylate is around 3, while histidine has a pKa around 6, so I was unsure whether that would prevent the attack from occurring.

Offline Babcock_Hall

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Re: Carboxylate attack Histidine Proton
« Reply #1 on: September 24, 2021, 11:38:07 AM »
There are some general principles to bear in mind.  One is that pKa values of side chains at the active site are often perturbed by several pH units.  Two is that questions like this are probably best approached on a case-by-case basis.  I studied the catalytic triad of a serine protease long ago.  What I found was that there was some evidence that the proton was unequally shared between a carboxylate and a histidine.
Mostly on the histidine, but in an unusual type of H-bond.
« Last Edit: September 24, 2021, 01:38:57 PM by Babcock_Hall »

Offline rolnor

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Re: Carboxylate attack Histidine Proton
« Reply #2 on: September 24, 2021, 01:05:53 PM »
Imidazole is a weak base so it will be a equilibrium but I think the proton will be more on the histidine.

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