CoFactor - FAQ

What is a cofactor?

A cofactor is a non-standard amino-acid small molecule that assists an enzyme in catalysis [IUPAC]. To exclude allosteric regulaters, we require a cofactor to be present in the active site. Cofactors can be inorganic molecules (e.g. metal ions), or organic molecules (e.g. PLP), which may somtimes be complexes with metal ions (e.g. heme). In the CoFactor database, we ai to gather information about these organic cofactors.

We classify organic cofactors on two levels. Firstly, we can distinguish the cofactor's mode of binding to its target enzyme. If the cofactor dissociates from the enzyme after each catalytic cycle, it is called a coenzyme [IUPAC] , otherwise it is a prosthetic group [IUPAC]. The latter can be covalently or non-covalently bound to the enzyme, but generally stays with he protein during all its (catalytically active) life time. Secondly, we can distinguish organic cofactors on their source in human metabolism. Some cofactors are vitamins [Wiki] for humans, i.e. they have to be acquired by a food source. Others can be biosynthesised by the human cell. A third category does not occur in human metabolism at all.

What is an E.C. number?

An E.C. number is the overall chemical transformation that an enzyme catalyses in a four level system. The levels are numbers separated by dots. The first level classifies the enzyme class, which describes the overall change in the reactants. The second and third numbers denote the sub-class and the sub-sub class, and describe the chemistry in ever greater detail. The last number is a serial number, which distingiushes all the enzymes in the same sub-sub-class and generally denotes the substrate specificity of the enzyme. Enzymes are classified by the Enzyme Commission.

What is the difference between an enzyme reaction and its mechanism?

An enzyme reaction is the chemical transformation from reactants to products, which is catalysed by an enzyme. There are diffent levels of detail on which one can describe enzyme reactions. The E.C. classification describes the overall transformation performed by the enzyme. The enzyme mechanism, however, can consist of several steps, and sometimes the same enzyme (as defined by its E.C. number) can have different machanisms to achieve the same overall transformation. For a database of enzyme mechansims, please refer to MACiE.

What is an E.C. wheel?

An E.C. wheel is a pie chart representation of a collection of related E.C. numbers. Each segment at the outer edge of the wheel represents a single EC number and the proportions of the wheel are determined by the number of entries on the outer edge.It can serve as a visual profile of which parts of the biochemical space these enzymes occupy. The six E.C. classes are coded in six different colours and each level of the E.C. classification is represented by one ring in the E.C. wheel. On this web server we include all those E.C. numbers in the E.C. wheels that have a primary literature, IntEnz, KEGG or MACiE entry as a reference source, but not the ones that have PDB or Procognate, because that latter might be only binding to the host protein but not catalytically active.

Here are two examples of E.C. wheels, showing all E.C. numbers on the left and all those E.C. number that we have identified as cofactor-using on the right. Please note that the black outer ring on the left E.C. wheel is a result of the high overall number of E.C. serial numbers.

What is an E.C. tree?

An E.C. tree represents all enzymes within the E.C. classification. A related set of enzymes can be highlighted by colour-coded thicker lines, in an analogous manner to the colour-coding in E.C. wheels. The tree represenation, like the E.C. wheel, shows the chemical space occupied by a set of enzymes, but also allows for a comparison to the whole of E.C. space. Like for the E.C. wheels, we include all those E.C. numbers in the E.C. trees that have a primary literature, IntEnz, KEGG or MACiE entry as a reference source, but not the ones that have PDB or Procognate, because that latter might be only binding to the host protein but not catalytically active.