1
$\begingroup$

I heard that some point mutations in proteins are OK, like from alanine to glycine (I'm not sure, it's just an example), some will change the protein significantly. I want to understand deeper but don't know the right keyword. I have tried some but none of them works. Can you give me a good keyword to start searching? Thank you.

$\endgroup$
  • 1
    $\begingroup$ Try googling "tolerated amino acid changes." The connection between amino acids, overall structure and function is complex, and not completely solvable. People can make guesses based on similarity between different amino acids, and can make better ones by consulting the protein structure, if it's known, but it's not possible to predict with total confidence that an amino acid change will be harmless or not. $\endgroup$ – swbarnes2 Jul 1 '14 at 18:49
3
$\begingroup$

As others have said, although certain amino acid substitutions are considered to be conservative, the effect of a particular substitution will very much depend upon the context. Here are some examples:

gly>ala can change stability of glyceraldehyde-3-phosphate dehydrogenase

gly>ala mutations in a fungal glucoamylase increase thermostability

asp>glu in a lysosomal α-glucosidase is responsible for a glycogen storage disease

asn>gln will abolish glycosylation at NXS/T sites which can have effects on stability and secretion

ser>thr at the active site has profound effects upon catalytic activity of an alkaline phosphatase

$\endgroup$
4
$\begingroup$

There are twenty standard amino acids, and some of them are structurally/functionally similar to each other, such as aspartate and glutamate, or asparagine and glutamine, or glycine and alanine. In general, mutations that cause these amino acid switches don't change the function of the protein, but that's just a general rule - it also depends on where these amino acids are in the protein structure. These are called conservative mutations.

$\endgroup$
2
$\begingroup$

I think you are referring to the concept of conserved substitution, which tends not to change the property/function (http://en.wikipedia.org/wiki/Sequence_alignment) of a protein although thats not necessarily true if the mutated AA (point mutation) changes a functional residue in an enzymatic domain such as GAP or kinase domains or even certain residues that are important for PP interactions such as tyrosine Y, which can become phosphorylated and thats important at times for its interaction with other proteins or the activation/inactivation status of a protein such as receptor tyrosine kinases (http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase). But in most cases it depends where the AA is and the role of the AA. For example two AA can have the same charge/polarity but if their sizes are considerably different, then that could interfere with the way protein folds (conformational changes) and end up affecting its function. So AA substitution and its effects is not necessarily straight forward and its very much dependent on other factors!

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.