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Motivation: Organic enzyme cofactors are involved in many enzyme reactions. Therefore, the analysis of cofactors is crucial to gain a better understanding of enzyme catalysis. To aid this, we have created the CoFactor database.
Results: CoFactor provides a web interface to access hand-curated data extracted from the literature on organic enzyme cofactors in biocatalysis, as well as automatically collected information. CoFactor includes information on the conformational and solvent accessibility variation of the enzyme-bound cofactors, as well as mechanistic and structural information about the hosting enzymes.
Availability: The database is publicly available and can be accessed at http://www.ebi.ac.uk/thornton-srv/databases/CoFactor
Supplementary information: Supplementary data are available at Bioinformatics online.
Enzymes are proteins that catalyze the repertoire of chemical reactions found in nature, and as such are vitally important molecules. They are generally composed of the 20 common amino acid residues, but many also require small molecules in addition for the catalysis to occur. In some cases, these molecules are involved in regulation or in ensuring the correct folding remote from the active site. However, many are termed cofactors, as they are required in the active site and are directly involved in catalysis. These cofactors may be either metal ions, whose involvement in catalysis we handle in Metal-MACiE (Andreini et al., 2009), or small organic molecules, which are described here. In both cases, these cofactors extend and enhance the basic catalytic toolkit of enzymes.
To date, there has been little collation of information on organic cofactors and their functions outside of the primary literature. CoFactor has been designed to remedy this, as MACiE (Holliday et al., 2007) and Metal-MACiE were designed to collate data on enzyme mechanisms and metal ions in catalysis, respectively.
The CoFactor database contains 27 entries for organic enzyme cofactors (see Supplementary Table S1). On the index page, the user can choose which cofactor entry to view. The left-hand navigation contains links to all the pages described, as well as to the home page, a glossary page, a contact form and a database statistics page. For each cofactor, the web site provides:
The data collection process used to populate the database is summarized in Figure 1.
All X-ray and NMR structures in the PDBe biological assemblies database (Boutselakis et al., 2003), which contain a HET group assigned to a cofactor, have been used for the superposition and solvent accessibility calculations. All instances of one cofactor HET group have been superimposed on a rigid part of the molecule. NACCESS (Hubbard and Thornton, 1993) was applied to compute the solvent accessibility of each atom a in each cofactor twice: first for the biological assembly (SAbiolAssembly(a)) and second for the cofactor alone SAcofactorAlone(a). The relative solvent accessibility of each atom a RSA(a) has been calculated as shown in below.
The mechanisms are based on all the information on a cofactor molecule in MACiE. All mechanisms have been visually inspected and all substrates and products have been abstracted to be reduced to the essential bonds that are involved in the reaction mechanism catalyzed by this cofactor.
The CoFactor database provides an overview for each organic enzyme cofactor. It integrates information on the organic compounds with protein structures, domains, sequences, enzyme reactions and mechanisms. These data can be used to learn about the tasks of cofactors in biocatalysis and an analysis of cofactor properties, structure and function is in progress (Fischer, J.D. et al., submitted for publication). Most of the cofactors have been known for many years, with very few recent discoveries. Therefore, we do not expect that this data resource will require major changes in the future.
Funding: European Molecular Biology Laboratory.
Conflict of Interest: none declared.