ZincBind-the database of zinc binding sites

Abstract

Zinc is one of the most important biologically active metals. Ten per cent of the human genome is thought to encode a zinc binding protein and its uses encompass catalysis, structural stability, gene expression and immunity. At present, there is no specific resource devoted to identifying and presenting all currently known zinc binding sites. Here we present ZincBind, a database of zinc binding sites and its web front-end. Using the structural data in the Protein Data Bank, ZincBind identifies every instance of zinc binding to a protein, identifies its binding site and clusters sites based on 90% sequence identity. There are currently 24 992 binding sites, clustered into 7489 unique sites. The data are available over the web where they can be browsed and downloaded, and via a REST API. ZincBind is regularly updated and will continue to be updated with new data and features.

Figure 1

The number of representatives in the largest 100 binding site clusters, ranked on the -axis by the number of sites in that cluster. Carbonic anhydrase, ranked first, can be seen as a clear outlier—it is very highly represented.

Figure 2

The distribution of liganding atom distances in all single-zinc sites, with a resolution better than 3Å. The overall distribution can be seen as bimodal, with the first peak being the preferred distance of nitrogen and oxygen, and the second peak being the preferred distance of sulphur, which has a greater Van der Waals radius. While nitrogen and sulphur both have tight distributions, oxygen does not, and has a much more prominent tail in its distribution.

Figure 3

(a) The active site of Cu,Zn Superoxide Dismutase (PDB entry 2SOD). Here a single histidine residue links a zinc atom and a copper atom into a single functional unit. (b) A three zinc co-active site taken from PDB entry 6A5K. Both images are taken from ZincBind.

Figure 4

The ZincBind home page. From here the user has the option of performing a ‘quick search’ of the entire database, without having to construct an advanced query on the advanced search page. The links in the navigation bar at the top offer quick access to this search functionality, as well as overviews of the data, browse options and help resources.

Figure 5

The ZincBind search page. This allows the user to search the database by a particular property, such as PDB title or resolution limit, and also offers the option to BLAST search the zinc-bearing chains in the database. On the resultant search page, there are options to sort the returned results by a number of metrics.

Figure 6

An example of a Zinc Binding Site on ZincBind. This provides an overview of the liganding residues, and the zinc atom(s) in this site. There are links to any equivalent sites that might exist in the database. Below this is a 3D, fully manipulable representation of the binding site, with customizable display options. Finally, there is a summary of the PDB structure from which the site is taken.