I am studying a protein which has Cysteine in position 261 and there are reports on PTM at this position and converting to oxoalanine.
There are other reports mention cys261arg mutation to be more common.
I wish to perform molecular dynamics simulations comparing native and mutant protein, in this case should i consider, 'cystine' as native or 'oxoalanine' as native?
In simple terms, can mutation occur after PTM or vice-versa?
Mutations work on the levels of the gene, they affect the DNA, from which the messenger-RNA is copied, which in turn tells the ribosome which amino acids to introduce into the protein. Therefore, mutations happen long before any protein is produced, and affect all copies of the protein produced from that gene. They occur before any posttranslational modifications can occur. By replacing the amino acid that would be modified or the recognition motif required by the enzyme introducing the posttranslational modifications, mutations can determine whether or not a given modification can be introduced into the protein.
Posttranslational modifications are introduced into the protein after it is produced. Frequently, posttranslational modifications play a regulatory role, either activating or inhibiting an enzyme.
e.g Human lysosomal arylsulfate A (ASA) is a member of the sulfatase family which requires the posttranslational oxidation of thiol group of a cysteine that is conserved among all eukaryotic sulfatases, yielding 2-formylglycine. (=Oxoalanine) (PMID: 9521684).
Which form of you protein you consider as "native" depends on the specific protein and the questions you want to answer with your dynamics simulation. If an enzyme requires a specific modification to fulfill its normal function, you would consider the modifies form as native. On the other hand, a modification that inactivates a protein or tags it for degradation would be be considered a secondary modification.
Mutations work on the levels of the gene, they affect the DNA, from which the messenger-RNA is copied, which in turn tells the ribosome which amino acids to introduce into the protein. Therefore, mutations happen long before any protein is produced, and affect all copies of the protein produced from that gene. They occur before any posttranslational modifications can occur. By replacing the amino acid that would be modified or the recognition motif required by the enzyme introducing the posttranslational modifications, mutations can determine whether or not a given modification can be introduced into the protein.
Posttranslational modifications are introduced into the protein after it is produced. Frequently, posttranslational modifications play a regulatory role, either activating or inhibiting an enzyme.
e.g Human lysosomal arylsulfate A (ASA) is a member of the sulfatase family which requires the posttranslational oxidation of thiol group of a cysteine that is conserved among all eukaryotic sulfatases, yielding 2-formylglycine. (=Oxoalanine) (PMID: 9521684).
Which form of you protein you consider as "native" depends on the specific protein and the questions you want to answer with your dynamics simulation. If an enzyme requires a specific modification to fulfill its normal function, you would consider the modifies form as native. On the other hand, a modification that inactivates a protein or tags it for degradation would be be considered a secondary modification.
PTMs are necessary for protein folding and therefore important for the function of protein. Improper PTMs at specific amino acid will affect the heterologous protein synthesis. This could be at a specific amino acid that is a hot spot for
Mutation, however the occurance of mutations at this amino acid or another is not necessarily linked to PTMs.
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