Spotting Cofactors in the PDB

Image of cofactor bound to protein
25 June 2018

Cofactors are an essential class of non-protein organic molecules. Among the many small molecules in the PDB archive, they’re now easier to identify.

Many enzymes can’t function without the presence of other, non-protein, molecules known as cofactors (or coenzymes). PDBe and Prof. Janet Thornton’s groups at EMBL-EBI have worked to annotate cofactors and cofactor-like molecules within the PDB archive, building on the Thornton group’s work in the CoFactor database.

We have identified 298 small molecules (mainly organic and metal-organic compounds) in the PDB chemical component dictionary which, based on the curated list of small molecule available from the CoFactor database, are likely to function as cofactors. That list of cofactor molecules has been expanded by identifying molecules in the PDB chemical component dictionary which are structurally similar. If one of these molecules is bound to an enzyme known to have a cofactor (as curated by the CoFactor database) we have annotated these molecules as a cofactor.

Cofactor information displayed on the PDBe entry page

Co-factors are now clearly identified in the ‘ligands and environments’ section of an entry page at PDBe. This information is also available via the PDBe REST API service and searchable through our Advanced Search.

Out of 70,540 PDB entries containing enzymes (ie, assigned an EC number), 12,000 contain cofactor or cofactor-like molecules and these represent more than 1,500 different enzyme classes. We can see that there is significant sequence and structural conservation as these enzymes are categorised into 574 Pfam domains and only 268 CATH domains.