- Glossary of Terms
- Introduction
- Splitting CCDs
- Merging CCDs
- Replacing CCDs
- Adding CCDs to Polypeptide Sequences
- Renaming CCDs
- Changing CCD Parents
- Acknowledgements
PCM - Protein chemical modification
PTM - Post-translational modification
The standardization of PCM handling ensures that there is a single correct approach to handling each PCM that occurs within the PDB archive. However, there are many existing PDB entries that contain PCMs which do not follow these handling conventions.
As part of the PCM remediation project, all entries containing protein modifications are being re-released to add the new PCM data category described here. During this process, any PCMs that are incorrectly handled within a PDB entry are amended to ensure that they are consistently handled.
In this document, some examples are provided describing the processes that are being performed to standardize PCM handling in PDB entries.
In some instances, a single peptide residue CCD is inconsistently used to describe a linked modification. For example, the CCD MYK describes N6-Myristoyl-Lysine, however, myristoylation is a lipid modification and must be handled as linked modification. In all entries that contain MYK the following splitting process must be performed:
| Existing CCD | > | New Peptide CCD | New Linked CCD | Example PDB Entry ID |
|---|---|---|---|---|
| MYK | > | LYS | MYR | 3U31 |
In some instances, a linked modification group is inconsistently used to describe a PCM that should be handled as a peptide residue within the polypeptide sequence. For example, phosphoserine can be inconsistently described using two CCDs, serine (SER) and phosphate (PO4) rather than the phosphoserine CCD (SEP). This is because this is a 'Named protein modification' and so should be handled as a single CCD describing both the peptide residue and modification group. The following merging process must be performed in all of these cases:
| Existing Peptide CCD | Existing Linked CCD | > | New CCD | Example PDB Entry ID |
|---|---|---|---|---|
| SER | PO4 | > | SEP | 6FW5 |
In some instances, a CCD ID is incorrectly used to describe a PCM where another existing CCD already describes the modification. One example of this is the use of CCDs to describe Heme (HEM) and Heme C (HEC). HEM should be used exclusively to describe non-covalently bound heme, whereas HEC should be used to describe covalently bound heme C. However, there are many entries in which these are inconsistently used. The following replacement process must be performed in all of these cases:
| Existing CCD | > | New CCD | Example PDB Entry ID |
|---|---|---|---|
| HEM | > | HEC | 19HC |
In some instances, a CCD is linked to the polypeptide rather than being part of the polypeptide sequence. This most often occurs to the terminal residues of the sequence and most commonly to the terminal caps ACE and NH2. The following addition process must be performed in all of these cases:
| CCD | Current Handling | > | New Handling | Example PDB Entry ID |
|---|---|---|---|---|
| ACE | Linked to peptide N-terminus | > | Part of peptide sequence | 1BHQ |
| NH2 | Linked to peptide C-terminus | > | Part of peptide sequence | 4TKY |
The opposite process can also occur, where a CCD should be removed from a polypeptide sequence. For example terminal myristoylation (MYR) is often inconsistently annotated as being part of the polypeptide sequence. The following removal process must be performed in all of these cases:
| CCD | Current Handling | > | New Handling | Example PDB Entry ID |
|---|---|---|---|---|
| MYR | Part of peptide sequence | > | Linked to peptide N-terminus | 2NA0 |
As part of the PCM remediation process, many CCDs that describe protein modifications are being renamed to make them more findable and remove ambiguities in their naming. For example, the CCD MLZ describes the methylation of the side chain nitrogen of lysine, currently it is named 'N-METHYL-LYSINE' however this name is misleading, implying that the methylation occurs on the backbone nitrogen rather than the side chain nitrogen. It will be renamed in the following process:
| CCD | Current Name | > | New Name | Example PDB Entry ID |
|---|---|---|---|---|
| MLZ | N-METHYL-LYSINE | > | N6-METHYL-LYSINE | 1IV8 |
This naming must be reflected in all entries that contain the CCD MLZ.
As part of the PCM remediation process, many CCDs that describe protein modifications are having their parent residues updated. For example, the CCD SOQ is the CCD that describes N-METHYL-ASPARTIC ACID, however it is currently annotated as not having a parent residue. It is a natural modification to Aspartic acid and so the parent residue will be changed to ASP. The parent will be updated in the following process:
| CCD | Current Parent | > | New Parent | Example PDB Entry ID |
|---|---|---|---|---|
| SOQ | None | > | ASP | 7AZ6 |
This change in parent must be reflected in all entries that contain the CCD SOQ.
The protein chemical modifications (PCMs) and post translational modifications (PTMs) remediation project is a wwPDB collaborative project carried out principally by PDBe at EMBL-EBI, and is funded by BBSRC grant number BB/V018779/1.