What might happen when proline is replaced by glutamine with respect to the structure of a protein? Since proline gives such a sharp bend to a protein, won't its replacement affect the structure of a protein dramatically? Similarly, what if Lysine replaces histidine? Has this particular replacement noticed in any other conditions? if so, please let me know.
Well, that depends how rigid the structure must be. With glutamine it will be more flexible. Also, the side chain is longer and charged.
With Lys replacing His the change won't be so drastic. Main problem may be length of the side chain again.
That is a general question you are asking. It really depends a lot on the position of the amino acid in the 3D structure of the protein. Suppose a enzyme is like a hairy ball with the unstructured C-terminus hanging out. The active site is somewhere in the N-termini. Now if you carry out hypothetical point mutations in the C-termini, you would see hardly any changes.
Glutamine has a high helix propensity and can be found in a lot of alpha helices..Mutating a glutamine to a proline here could potentially disrupt helix formation. While switching it to a lysine might increase helix forming propensity. But, these generalizations are tricky unless you know the flanking sequences. For example, engineering a single switch from proline to glutamine in a Proline flanked region will not give you a considerable increase in helix propensities..
Lastly, Glutamine is uncharged and replacing it with lysine introduces a positive charge. This may/may not have implications on the protein. If the glutamine resides in the active site of the enzyme, it could affect its activity. If it lies in the membrane binding domain of the protein, it could enhance binding to negatively charged membranes.
Hope this helps..
Dear Shambhu,
As Aditya rightly mentioned, the effect of these mutation would be very much context dependent. P is a both helix and sheet breaker. So if you replace P with Q in some secondary structure region you might expect an increase in the stability of that region (of course flanking amino acids would also be important).
Changing H with K again is context dependent. If H is present in the interior of a protein, its replacement with K might lead to destabilization of the protein (as you are bringing positive charge in the interior of the protein). If H is exposed, you might not see a drastic effect upon its replacement with K. The effects will also depend upon the pKa of H in a given protein.
All in all, the effects of these mutations would be very much context dependent and it's difficult to generalize them.
Best,
Jogender
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