Editing Protein primary structure (section)

===Cleavage and ligation===
In addition to those listed above, the most important modification of primary structure is [[proteolysis|peptide cleavage]] (by chemical [[hydrolysis]] or by [[protease]]s). Proteins are often synthesized in an inactive precursor form; typically, an N-terminal or C-terminal segment blocks the [[active site]] of the protein, inhibiting its function. The protein is activated by cleaving off the inhibitory peptide.

Some proteins even have the power to cleave themselves. Typically, the hydroxyl group of a serine (rarely, threonine) or the thiol group of a cysteine residue will attack the carbonyl carbon of the preceding peptide bond, forming a tetrahedrally bonded intermediate [classified as a hydroxyoxazolidine (Ser/Thr) or hydroxythiazolidine (Cys) intermediate]. This intermediate tends to revert to the amide form, expelling the attacking group, since the amide form is usually favored by free energy, (presumably due to the strong resonance stabilization of the peptide group). However, additional molecular interactions may render the amide form less stable; the amino group is expelled instead, resulting in an ester (Ser/Thr) or thioester (Cys) bond in place of the peptide bond. This chemical reaction is called an [[N-O acyl shift]].

The ester/thioester bond can be resolved in several ways:
* Simple hydrolysis will split the polypeptide chain, where the displaced amino group becomes the new N-terminus. This is seen in the maturation of glycosylasparaginase.
* A β-elimination reaction also splits the chain, but results in a pyruvoyl group at the new N-terminus. This pyruvoyl group may be used as a covalently attached catalytic cofactor in some enzymes, especially decarboxylases such as [[S-adenosylmethionine decarboxylase]] (SAMDC) that exploit the electron-withdrawing power of the pyruvoyl group.
* Intramolecular transesterification, resulting in a ''branched'' polypeptide. In [[intein]]s, the new ester bond is broken by an intramolecular attack by the soon-to-be C-terminal asparagine.
* Intermolecular transesterification can transfer a whole segment from one polypeptide to another, as is seen in the Hedgehog protein autoprocessing.