BRITE enables the user to search any terms of interest, including enzymes, from many classifications at

a time. EC numbers (IUBMB Enzyme List), RC numbers (KEGG RCLASS) and K numbers (KEGG Orthology; KO) are the three main identifiers that classify enzymes, and all are available in KEGG BRITE. KO is a collection of the groups of orthologous genes that are regarded to share common function and the same evolutional origin, in other words, an orthology corresponds to a functional unit located in the same place in a reference pathway and phylogenetic tree. KO entries are generated in the process of genome annotation, and a KO entry in principle corresponds to more than one gene derived from more than one organism. In order to cope with an increasing number of complete genomes, the genome-based annotation is now automatically performed (except for a selected Selleckchem GSK458 number of reference organisms) with continuous efforts to manually improve the pathway-based, cross-species annotation. For predictive genomic and metabolomic analyses, it is essential to organize knowledge Epacadostat manufacturer about the relationships between enzyme structures (including amino acid sequences, and 3D structures) and enzyme functions. The process to classify amino acid sequences and 3D structures of proteins is performed by both manual annotations and automatic calculations. Both ways have advantages and disadvantages: the former is generally high in quality but low

in speed, and vise versa for the latter. Thus many databases apply the large-scale calculations followed by manual inspections. We propose that RCLASS contributes

to the large-scale calculation of reaction classification that efficiently integrates genomic and chemical spaces. The strength of our approach lies on the independence of reaction classification from the classification of enzyme genes, enzyme proteins and enzyme nomenclature. Due to this independence, it has become possible to cover all reactions by considering the differences among orthologous proteins in the range of substrate specificity, co-factor requirements, multistep reactions, multi-functional enzymes etc. For example, the enzymes EC 2.7.1.1 and EC 2.7.1.2 are defined as hexokinase and glucokinase, respectively. The former enzyme takes a broad range of molecules as substrates, catalyzing Protein kinase N1 many reactions (ATP+d-hexose=ADP+d-hexose 6-phosphate). One of them (ATP+d-glucose=ADP+d-glucose 6-phosphate) is catalyzed by the latter, with stricter substrate specificity. In KEGG, these two are regarded as the same type of reaction in terms of their RCLASS entries, and are grouped into three orthologue groups: an orthologue group K00844 is assigned to the former, and two orthologue groups K12407 and K00845 are assigned to the latter. In another example, there are three glyceraldehyde-3-phosphate (GAP) dehydrogenases with different cofactor requirements. EC 1.2.1.12 requires NAD+, EC 1.2.1.