[Ahmed Abdullah]

What is the Relationship between working PH of a protein (having native structure) and it's PI.
I think ;PI of a protein should be close to it’s working PH, otherwise it will be in wrong conformation. But I don't have any clear-cut idea about why it should be like that.
Please help.   

[Arkcon]

I think you've come to the wrong conclusions, which is why you may be having trouble finding confirmation of your point of view.  Suggestion:  define pI for us.  What does it really mean?  What does your book say happens to a protein at the pI?  Assuming the protein in question is an enzyme, can you find an example of an enzyme at work?  Working through these will help you learn, and you'll write better examination answers, when the time comes.

[wpenrose]

There is no necessary relationship between pI and optimum pH. Look up the definitions. Most proteins have pI's in the acid range, but the optimum pH is often near neutral (or it can be anything at all).

DB

[Ahmed Abdullah]

When the working PH is far away from the PI, the protein will be highly charged. That's why I  think large deviation from the PI will tend to minimize the folding, which is essential for its function. Globular proteins remain in highly folded state, so deviation from  PI should have higher influence on them.

Any comments..

[lancenti]

It actually depends on the kind of protein since being isoelectronic may actually mean that the folding is increased. Also, as far as I'm aware, amino acids are least soluble at its pI because of the overlapping hydration spheres. This might not be the case for proteins, but it might be a consideration for your line of thinking.

[Arkcon]

When the working PH is far away from the PI, the protein will be highly charged. That's why I  think large deviation from the PI will tend to minimize the folding, which is essential for its function. Globular proteins remain in highly folded state, so deviation from  PI should have higher influence on them.

Any comments..

Incorrect.  The "best" folding is not achieved at pI, that is for sure.  By definition, which you should look up in a college level textbook, to get all the nuances, pI is the point when all native charged side groups are uncharged. This will remove all folding, except by covalent linkages.  This will most likely ruin catalytic activity.  Often, at pI, the protein associates best with itself, and precipitates out, as a solid, and may not even refold properly when the pH is changed back.  Like wpenrose: said, you can't make predictions on optimal catalytic pH based on pI, or distance from it.

[sorry, I hit edit instead of quote - Yggdrasil]

[Yggdrasil]

pI is the point when all native charged side groups are uncharged.

This is incorrect.  The pI is the pH at which the protein has no net charge.  The side chains can be charged (e.g. under what conditions could you protonate a carboxylic acid with pKa ~3 but deprotonate an ammonium with pKa ~9?), but the number of positively charged groups are equal to the number of negatively charged groups.  Placing a protein at its pI will not necessarily prevent its folding as many aspects of protein folding do not depend highly on the charges of side chains.

[Arkcon]

Gah.  I did oversimplify, and muddled the answer.  At any rate:

will tend to minimize the folding, which is essential for its function

is getting the structure/function relationship of proteins wrong. Original poster did say, after all:

PI of a protein should be close to it’s working PH