Isopeptide bond: Difference between revisions

An ''isopeptide bond'' is an [http://en.wikipedia.org/wiki/Amide amide bond] between the sidechain of one [[amino acid]] and the sidechain or main chain terminus of another amino acid, or a ligand. Isopeptide bonds are sometimes called [http://en.wikipedia.org/wiki/Lactam lactams]<ref name="lactam">PMID: 24446383</ref><ref name="5vbl">PMID: 28528775</ref>.<br>[[Image:Isopeptide-bond.jpg|300px]]

Isopeptide bonds can form covalent links between polypeptide backbones. This is in contrast to the much more common [[Peptide bond|peptide (''eupeptide'') bonds]] between amino acid main chain atoms that form the polypeptide backbones of proteins. Isopepide bonds are rare (as are other non-disulfide [[protein crosslinks]]). [[Disulfide bonds]] are a much more common form of covalent linkage between polypeptide chains.

A search for ''isopeptide bond'' in the keywords records at the [[PDB]] returns about 200 hits (April, 2021). This suggests that approximately one model per thousand in the [[PDB]] contains isopeptide bonds. However, not all entries containing the term ''isopeptide'' actually have isopeptide bonds in the [[asymmetric unit]], and some entries that do have isopeptide bonds do not contain the word "isopeptide" anywhere in their PDB files.

In July, 2021, use of these records is inconsistent. Sometimes one is used, sometimes the other, sometimes some isopeptide bonds are in REMARK 500 CLOSE CONTACTS and other isopeptide bonds in the same model are in LINK records ([[5i6a]]), and sometimes isopeptide bonds that are present are not documented in either kind of record (e.g. [[1fma]] in July, 2021). In 2021, the [[wwPDB]] is considering remediation to properly annotate all isopeptide bonds<ref name="annotation">Remediation of the PDB database to guarantee proper annotation of all isopeptide bonds was discussed with Rachel Kramer Green of the RCSB in June, 2021.</ref>. See example PDB IDs below.

Note that link records involving MSE ([[selenomethionine]]) generally signify nothing more than MSE being part of a polypeptide chain, but are required because the [[Hetero atoms|HETATM]] MSE residue is covalently linked to the adjacent standard amino acids. Similarly, all covalent connections to D-amino acids [[5i6a]] and ligands should be listed in LINK records.

Isopeptide bonds in the following examples were specified in '''neither''' REMARK 500 CLOSE CONTACTS/_pdbx_validate_close_contact '''nor''' LINK/_struct_conn records in May, 2021<ref name="annotation" />. Subsequently, after being reported to the [[wwPDB]], these may have been remediated, which will be indicated in REVDAT/_database_PDB_rev records.

===Pyroglutamate===

N-terminal Glu or Gln can cyclize, forming an internal lactam (isopeptide) bond. See [http://en.wikipedia.org/wiki/Pyroglutamic_acid Pyroglutamic acid in Wikipedia]. Examples with convincing electron densities include [[1s1a]] (PCA1) and [[2are]] (Gln1). Element color key:

 

 

[[FirstGlance in Jmol]] alerts you to isopeptide bonds when present, and provides convenient links to that zoom and and display each one in detail. Viewing the [[electron density map]] is just one more click. Use the links above under ''Examples'' to go to a Proteopedia page titled with a 4-character [[PDB code]]. There, click on "FirstGlance". In FirstGlance, click on the Tools tab, and there, on "Protein Crosslinks". See the practical guide [[FirstGlance/Evaluating Protein Crosslinks]].