[helplessnerd0402]

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.

[Babcock_Hall]

There are some general principles to bear in mind.  One is that pK_a 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.

[rolnor]

Imidazole is a weak base so it will be a equilibrium but I think the proton will be more on the histidine.