Database Commons

a catalog of worldwide biological databases

Enzymes are basically composed of 20 naturally occurring amino acids, yet they catalyse a dizzying array of chemical reactions, with regiospecificity and stereospecificity and under physiological conditions. In this review, we attempt to gain some understanding of these complex proteins, from the chemical versatility of the catalytic toolkit, including the use of cofactors (both metal ions and organic molecules), to the complex mapping of reactions to proteins (which is rarely one-to-one), and finally the structural complexity of enzymes and their active sites, often involving multidomain or multisubunit assemblies. This work highlights how the enzymes that we see today reflect millions of years of evolution, involving de novo design followed by exquisite regulation and modulation to create optimal fitness for life.

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.

Many crucial biochemical reactions in the cell require not only enzymes for catalysis but also organic cofactors or metal ions. Here, we analyse the physicochemical properties, chemical structures and functions of organic cofactors. Based on a thorough analysis of the literature complemented by our quantitative characterisation and classification, we found that most of these molecules are constructed from nucleotide and amino-acid-type building blocks, as well as some recurring cofactor-specific chemical scaffolds. We show that, as expected, organic cofactors are on average significantly more polar and slightly larger than other metabolites in the cell, yet they cover the full spectrum of physicochemical properties found in the metabolome. Furthermore, we have identified intrinsic groupings among the cofactors, based on their molecular properties, structures and functions, that represent a new way of considering cofactors. Although some classes of cofactors, as defined by their physicochemical properties, exhibit clear structural communalities, cofactors with similar structures can have diverse functional and physicochemical profiles. Finally, we show that the molecular functions of the cofactors not only may duplicate reactions performed by inorganic metal cofactors and amino acids, the cell's other catalytic tools, but also provide novel chemistries for catalysis.