MetalPDB in 2018: a database of metal sites in biological macromolecular structures

Abstract

MetalPDB (http://metalweb.cerm.unifi.it/) is a database providing information on metal-binding sites detected in the three-dimensional (3D) structures of biological macromolecules. MetalPDB represents such sites as 3D templates, called Minimal Functional Sites (MFSs), which describe the local environment around the metal(s) independently of the larger context of the macromolecular structure. The 2018 update of MetalPDB includes new contents and tools. A major extension is the inclusion of proteins whose structures do not contain metal ions although their sequences potentially contain a known MFS. In addition, MetalPDB now provides extensive statistical analyses addressing several aspects of general metal usage within the PDB, across protein families and in catalysis. Users can also query MetalPDB to extract statistical information on structural aspects associated with individual metals, such as preferred coordination geometries or aminoacidic environment. A further major improvement is the functional annotation of MFSs; the annotation is manually performed via a password-protected annotator interface. At present, ∼50% of all MFSs have such a functional annotation. Other noteworthy improvements are bulk query functionality, through the upload of a list of PDB identifiers, and ftp access to MetalPDB contents, allowing users to carry out in-depth analyses on their own computational infrastructure.

Figure 1.

The Sequence tab for entry 12ca_2 (16). The new Sequence tab displays the sequence alignment of all proteins in the same superfamily. The proteins are grouped based on the relationship of their MFSs to the query MFS (equivalent or equistructural sites), whereas for proteins lacking any metal in the site the grouping is based on the conservation of the metal ligands (apo-structures with or without the metal-binding pattern). The metal ligands have a yellow background; the residues belonging to the MFS have a cyan background. H-bonded residues are highlighted in red.

Figure 2.

The summary page of 1joi_1 (17). The new Information on the site table reports the Physiological relevance of the site (highlighted with a red circle). Each physiological site has an associated function that is detailed in a further new table (Information on the function(s) of the site, also highlighted with a red circle) When an annotation is based on the literature, it is possible to display the sentence of the article that supports the functional annotation by hovering the mouse on the book icon. The book icon links to the article entry on PubMed.

Figure 3.

Example of statistics for zinc coordination spheres in the PDB. The information is accessible from the ‘Per metal’ statistics menu. (A) Pie chart displaying the coordination geometries of zinc sites; (B) histogram reporting the occurrence of residues in the first coordination sphere of zinc ions; (C) distances between zinc ions and different donor atoms.