Automatic assignment of EC numbers

Abstract

A wide range of research areas in molecular biology and medical biochemistry require a reliable enzyme classification system, e.g., drug design, metabolic network reconstruction and system biology. When research scientists in the above mentioned areas wish to unambiguously refer to an enzyme and its function, the EC number introduced by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (IUBMB) is used. However, each and every one of these applications is critically dependent upon the consistency and reliability of the underlying data for success. We have developed tools for the validation of the EC number classification scheme. In this paper, we present validated data of 3788 enzymatic reactions including 229 sub-subclasses of the EC classification system. Over 80% agreement was found between our assignment and the EC classification. For 61 (i.e., only 2.5%) reactions we found that their assignment was inconsistent with the rules of the nomenclature committee; they have to be transferred to other sub-subclasses. We demonstrate that our validation results can be used to initiate corrections and improvements to the EC number classification scheme.

Figure 1. Processes for reconstruction of a metabolic network.

Figure 2. Examples for the different subsets.

(a) The reverse direction of the reaction is shown. (b) Ambiguous, fits more than one sub-subclass. (c) Reaction is assigned to a wrong sub-subclass. (d) The enzyme catalysis two or more different types of reaction, where at least one does not meet the requirements of the assigned sub-subclass.

Figure 3. Examples for the different subsets.

(a) Unclear assignment (b) Ambiguous, fits two or more quite similar sub-subclasses. (c) Does not fit any defined sub-subclass. (d) Different sub-subclasses assigned, based on the identical reaction.

Figure 4. The complete procedure is demonstrated for the reaction catalysed by the enzyme indolelactate dehydrogenase (EC 1.1.1.110).

(a) In the first step the known reaction pairs NAD⁺/NADH and accordingly NAD⁺/H⁺ are identfied and removed from further calculation steps. (b) The functional groups within the remaining molecules are identified (c), counted and eliminated in the case if they are equal in number. (d) For each remaining group a distinct key is assigned. (e) Finally, a difference key of the overall reaction is generated.