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The primary structure of a peptide or protein is the linear sequence of its amino acid structural units, and partly comprises its overall biomolecular structure. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. ==Primary structure of polypeptides== In general, polypeptides are unbranched polymers, so their primary structure can often be specified by the sequence of amino acids along their backbone. However, proteins can become cross-linked, most commonly by disulfide bonds, and the primary structure also requires specifying the cross-linking atoms, e.g., specifying the cysteines involved in the protein's disulfide bonds. Other crosslinks include desmosine. The chiral centers of a polypeptide chain can undergo racemization. In particular, the L-amino acids normally found in proteins can spontaneously isomerize at the :The positive charge on the N-terminal amino group may be eliminated by changing it to an acetyl group (N-terminal blocking). * formylation :The N-terminal methionine usually found after translation has an N-terminus blocked with a formyl group. This formyl group (and sometimes the methionine residue itself, if followed by Gly or Ser) is removed by the enzyme deformylase. * pyroglutamate :An N-terminal glutamine can attack itself, forming a cyclic pyroglutamate group. * myristoylation :Similar to acetylation. Instead of a simple methyl group, the myristoyl group has a tail of 14 hydrophobic carbons, which make it ideal for anchoring proteins to cellular membranes. The C-terminal carboxylate group of a polypeptide can also be modified, e.g., * amidation (see Figure) :The C-terminus can also be blocked (thus, neutralizing its negative charge) by amidation. * glycosyl phosphatidylinositol (GPI) attachment :Glycosyl phosphatidylinositol is a large, hydrophobic phospholipid prosthetic group that achors proteins to cellular membranes. It is attached to the polypeptide C-terminus through an amide linkage that then connects to ethanolamine, thence to sundry sugars and finally to the phosphatidylinositol lipid moiety. Finally, the peptide side chains can also be modified covalently, e.g., * phosphorylation :Aside from cleavage, phosphorylation is perhaps the most important chemical modification of proteins. A phosphate group can be attached to the sidechain hydroxyl group of serine, threonine and tyrosine residues, adding a negative charge at that site and producing an unnatural amino acid. Such reactions are catalyzed by kinases and the reverse reaction is catalyzed by phosphatases. The phosphorylated tyrosines are often used as "handles" by which proteins can bind to one another, whereas phosphorylation of Ser/Thr often induces conformational changes, presumably because of the introduced negative charge. The effects of phosphorylating Ser/Thr can sometimes be simulated by mutating the Ser/Thr residue to glutamate. * glycosylation :A catch-all name for a set of very common and very heterogeneous chemical modifications. Sugar moieties can be attached to the sidechain hydroxyl groups of Ser/Thr or to the sidechain amide groups of Asn. Such attachments can serve many functions, ranging from increasing solubility to complex recognition. All glycosylation can be blocked with certain inhibitors, such as tunicamycin. * deamidation (succinimide formation) :In this modification, an asparagine or aspartate side chain attacks the following peptide bond, forming a symmetrical succinimide intermediate. Hydrolysis of the intermediate produces either asparate or the β-amino acid, iso(Asp). For asparagine, either product results in the loss of the amide group, hence "deamidation". * hydroxylation : Proline residues may be hydroxylates at either of two atoms, as can lysine (at one atom). Hydroxyproline is a critical component of collagen, which becomes unstable upon its loss. The hydroxylation reaction is catalyzed by an enzyme that requires ascorbic acid (vitamin C), deficiencies in which lead to many connective-tissue diseases such as scurvy. * methylation Several protein residues can be methylated, most notably the positive groups of lysine and arginine. Methylation at these sites is used to regulate the binding of proteins to nucleic acids. Lysine residues can be singly, doubly and even triply methylated. Methylation does ''not'' alter the positive charge on the side chain, however. * acetylation : Acetylation of the lysine amino groups is chemically analogous to the acetylation of the N-terminus. Functionally, however, the acetylation of lysine residues is used to regulate the binding of proteins to nucleic acids. The cancellation of the positive charge on the lysine weakens the electrostatic attraction for the (negatively charged) nucleic acids. * sulfation Tyrosines may become sulfated on their The hydrophobic isoprene (e.g., farnesyl, geranyl, and geranylgeranyl groups) and palmitoyl groups may be added to the atom of cysteine residues to anchor proteins to cellular membranes. Unlike the GPI and myritoyl anchors, these groups are not necessarily added at the termini. * carboxylation :A relatively rare modification that adds an extra carboxylate group (and, hence, a double negative charge) to a glutamate side chain, producing a Gla residue. This is used to strengthen the binding to "hard" metal ions such as calcium. * ADP-ribosylation The large ADP-ribosyl group can be transferred to several types of side chains within proteins, with heterogeneous effects. This modification is a target for the powerful toxins of disparate bacteria, e.g., ''Vibrio cholerae'', ''Corynebacterium diphtheriae'' and ''Bordetella pertussis''. * ubiquitination and SUMOylation Various full-length, folded proteins can be attached at their C-termini to the sidechain ammonium groups of lysines of other proteins. Ubiquitin is the most common of these, and usually signals that the ubiquitin-tagged protein should be degraded. Most of the polypeptide modifications listed above occur ''post-translationally'', i.e., after the protein has been synthesized on the ribosome, typically occurring in the endoplasmic reticulum, a subcellular organelle of the eukaryotic cell. Many other chemical reactions (e.g., cyanylation) have been applied to proteins by chemists, although they are not found in biological systems. ===Modifications of primary structure=== In addition to those listed above, the most important modification of primary structure is peptide cleavage (See: Protease). Proteins are often synthesized in an inactive precursor form; typically, an N-terminal or C-terminal segment blocks the 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 inteins, 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. " TITLE="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 (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 inteins, 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. ">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 (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 inteins, 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. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「protein primary structure」の詳細全文を読む スポンサード リンク
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