Isopeptide bond: Difference between revisions

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Eric Martz, Joel L. Sussman

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-An ''isopeptide bond'' is an [https://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 [https://en.wikipedia.org/wiki/Lactam lactams]<ref name="lactam">PMID: 24446383</ref>.
+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]]
-<br>[[Image:Isopeptide-bond.jpg|300px]]
-Isopeptide bonds often 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 [[lysine-cysteine NOS bonds]]). [[Disulfide bonds]] are a much more common form of covalent linkage between polypeptide chains.
+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.
 For more, please see [http://en.wikipedia.org/wiki/Isopeptide_bond Isopeptide bond in Wikipedia].
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 ==Frequency==
-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 mention this anywhere in their PDB files.
+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.
-==PDB KEYWDS and LINK Records==
+==PDB KEYWDS, REMARK 500, and LINK Records==
-Structures containing isopeptide bonds usually have "ISOPEPTIDE BOND" in their PDB file KEYWDS record, and sometimes have LINK records (or _struct_conn in their [[Atomic coordinate file|mmCIF]] files) specifying the isopeptide-bonded residues. Here are the relevant LINK records from [[3htl]]:<pre>
+Structures containing isopeptide bonds sometimes have "ISOPEPTIDE BOND" in their PDB file KEYWDS record. More importantly, many list isopeptide bonds in detail in either of the following two records:
+{| class="wikitable"
+|+ Isopeptide Bond Specifications
+|-
+! PDB Format !! mmCIF Format
+|-
+| REMARK 500 || _pdbx_validate_close_contact
+|-
+| LINK || _struct_conn
+|}
+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.
+Here is an example of the relevant REMARK 500 records from [[2xi9]]. The lines with ATM1=NZ are isopeptide bonds; those with ATM1=SG are [[Thioester protein crosslinks|thioester bonds]].<pre>
+REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
+REMARK 500
+REMARK 500  ATM1  RES C  SSEQI   ATM2  RES C  SSEQI           DISTANCE
+REMARK 500   NZ   LYS B   297     CG   ASP B   595              1.31
+REMARK 500   NZ   LYS A   297     CG   ASP A   595              1.32
+REMARK 500   SG   CYS B   426     CD   GLN B   575              1.63
+REMARK 500   SG   CYS A   426     CD   GLN A   575              1.64</pre>
+Here are the relevant LINK records from [[3htl]]:<pre>
 LINK         NZ  LYS X 199                 CG  ASN X 321     1555   1555  1.43
 LINK         NZ  LYS X 363                 CG  ASN X 482     1555   1555  1.55</pre>
-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.
+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.
-===Unspecified Isopeptide Bonds===
-Some structures that contain isopeptide bonds lack LINK/_struct_conn records specifying these bonds. See examples below. In June, 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>.
 ==Examples==
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 *The capsid of the HK97 bacteriophage contains isopeptide bonds that cross-link the protein [[chains]] into a protein '''chain mail''' <ref>PMID: 22297521</ref><ref>PMID: 10572124</ref><ref name="wikoff2000">PMID: 19091865</ref>. However, these do not occur in the [[asymmetric unit]] of [[1ohg]]<ref>PMID: 11000116</ref>. They can be visualized in the [[biological unit]], which is the full virus capsid, but that is technically challenging.
 * [[7cap]] is a ubiquitin homotrimer. [[3alb|3ALB]] is a ubiquitin homotetramer. In both cases, the <b>C-terminal</b> Gly76 is isopeptide linked to Lys48 in each '''inter-chain''' interface<ref name="hiranyakorn" />.
-* [[4mli]] contains the SpyTag peptide (which can be linked to a protein of interest) forming an isopeptide bond between SpyTag peptide Lys31 and SpyCatcher protein Asp117<ref>PMID: 24161952</ref>.
+* [[4mli]] contains the '''SpyTag peptide''' (which can be linked to a protein of interest) forming an isopeptide bond between SpyTag peptide Lys31 and SpyCatcher protein Asp117<ref>PMID: 24161952</ref>.
 * [[3htl]] is a pilus monomer with spontaneously-formed <b>intra-chain</b> isopeptide bonds Lys199-Asn321 and Lys363-Asn482<ref>PMID: 19805181</ref>. (Pilin chains form enzymatically, linked by the isopeptide Lys169 sidechain bonded to the carboxy terminus Thr494. Those inter-chain isopeptide bonds are not present in the monomer structure.)
 * [[6vzx]]: triple helix formed from collagen-mimetic peptides, stabilized by Lys11-Glu13 inter-chain isopeptide bonds.
+* [[5i6a]]: 10-amino acid peptides with both '''N-terminal''' and '''C-terminal''' isopeptide bonds, some involving [[Amino_Acids#L-_and_D-Amino_Acids|D-amino acids]].
 ===Unspecified===
-Isopeptide bonds in the following examples were '''not''' specified in LINK/_struct_conn records in May, 2021<ref name="annotation" />.
+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.
 *[[1fma]]: Molybdopterin synthase, an enzyme with structural similarity to ubiquitin, has Lys118 chain E isopeptide bonded to the carboxy-terminal Gly81 in chain D.
 *[[5jqf]]: Lasso peptide sphingopyxin I has Asp9 isopeptide bonded to the amino terminus at Gly1. This bond is cleaved by lasso peptide isopeptidase.
-==Visualization==
+===Pyroglutamate===
+[[Image:2are-gln1-chain-A-225px.png|right|frame|Pyroglutamate with electron density map]]
+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:
+{{Template:ColorKey_Element_C}}
+{{Template:ColorKey_Element_O}}
+{{Template:ColorKey_Element_N}}.
+==Detection and Visualization==
-Version 3.3 of [[FirstGlance in Jmol]] (not yet released in May, 2021) alerts you to isopeptide binds, and provides links to visualize each one conveniently. Use the links above under ''Examples'' to go to a Proteopedia page titled with a [[PDB code]]. There, click on "FirstGlance". In FirstGlance, click on "Show more details" in the
+[[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]].
-[http://firstglance.jmol.org/where.htm#mit Molecule Information Tab]. Look for "Isopeptide bonds" in the
-[http://firstglance.jmol.org/where.htm#mit Molecule Information Tab].
 ==Other Types of Protein Crosslinks==