Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: helplessnerd0402 on September 24, 2021, 10:32:01 AM
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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.
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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.
EDT
Mostly on the histidine, but in an unusual type of H-bond.
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Imidazole is a weak base so it will be a equilibrium but I think the proton will be more on the histidine.