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International Union of Biochemistry [now termed the International Union of
Biochemistry and Molecular Biology (IUBMB)] set up the Enzyme Commission
(EC) for providing a systematic approach to the naming of enzymes and published
first report in 1961. The sixth edition, published in 1992, contained details of nearly
3200 different enzymes, and supplements published annually have now extended
this number to over 5000 (Robinson 2015). The E.C. number classification is a four
level hierarchical system of an enzyme’s overall reaction or function. The E.C. first
level corresponds to six classes according to the type of reaction being carried out
includes oxidoreductases catalyze oxidation/reduction reactions (EC 1), transferases transfer a chemical group (EC 2), hydrolases perform hydrolysis of chemical
bonds (EC 3), lyases also cleave chemical bonds by other means than by oxidation
or hydrolysis (EC 4), isomerases catalyze geometric and structural changes between
isomers (EC 5), and ligases joins two compounds with associated hydrolysis of a
nucleoside triphosphate molecule (EC6). The next two classification levels are subclass and sub-sub-class (level 2 and level 3) depends on a various criteria such as
chemical bond cleaved or formed, the reaction center, the transferred chemical
group or the cofactor used for catalysis. The final level (fourth) gives a serial number for each enzyme reaction, substrate specificity. One E.C. number denotes an
overall chemical reaction of an enzyme. Thus, several enzymes, which may be nonhomologous, may be identified by the same E.C. number if they catalyze the same
overall reaction. For example, the enzyme with the trivial name lactate dehydrogenase has the EC number 1.1.1.27, is an oxidoreductase (indicated by the first digit)
with the alcohol group of the lactate molecule as the hydrogen donor (second digit)
and NAD+ as the hydrogen acceptor (third digit), and is the 27th enzyme to be categorized within this group (fourth digit). The basic E.C. number classification layout of enzymes is described in Table 1.
The EC classification is still made on the basis of main reaction being catalyzed
(Cuesta et al. 2015). Nowadays the assignment of EC numbers to enzyme is a common routine in the functional annotation of proteins and protein-coding genes in
databases such as UniprotKB (UniProt Consortium 2013) and Ensembl (Kersey
et al. 2014) and has been adopted by the widely uses Gene Ontology (GO)
(Ashburner et al. 2000). However possible changes between EC classes are observed.
There are some preferences such as transferases (EC 2) becoming oxidoreductases
(EC 1), hydrolases (EC 3) and lyases (EC 4) (Martınez Cuesta et al. 2014).
Exchanges between different EC classes suggest that the chemistry of enzymes is
more complex than previously classified with close relationships between enzymes
with radically different EC numbers. The substrate specificity of enzyme is represented by the last digit of the EC number, while the first three digits describe the
type of the reaction. In case the sequence identity is below 70%, all the four digits
of the EC number start to diverge quickly (Rost 2002). This creates an urgent need
to choose alternative methods to sub-group enzymes that reflects their function or
substrate specificity. The chemistry of related enzyme functions can now be explored
using robust computational approaches like EC-BLAST (Rahman et al. 2014). This
tool searches and compares reactions on the basis of bond charges, reaction centers,
and structures of substrates and products (Cuesta et al. 2015; Rausch et al. 2005).
Proteins as Enzymes
International Union of Biochemistry [now termed the International Union of
Biochemistry and Molecular Biology (IUBMB)] set up the Enzyme Commission
(EC) for providing a systematic approach to the naming of enzymes and published
first report in 1961. The sixth edition, published in 1992, contained details of nearly
3200 different enzymes, and supplements published annually have now extended
this number to over 5000 (Robinson 2015). The E.C. number classification is a four
level hierarchical system of an enzyme’s overall reaction or function. The E.C. first
level corresponds to six classes according to the type of reaction being carried out
includes oxidoreductases catalyze oxidation/reduction reactions (EC 1), transferases transfer a chemical group (EC 2), hydrolases perform hydrolysis of chemical
bonds (EC 3), lyases also cleave chemical bonds by other means than by oxidation
or hydrolysis (EC 4), isomerases catalyze geometric and structural changes between
isomers (EC 5), and ligases joins two compounds with associated hydrolysis of a
nucleoside triphosphate molecule (EC6). The next two classification levels are subclass and sub-sub-class (level 2 and level 3) depends on a various criteria such as
chemical bond cleaved or formed, the reaction center, the transferred chemical
group or the cofactor used for catalysis. The final level (fourth) gives a serial number for each enzyme reaction, substrate specificity. One E.C. number denotes an
overall chemical reaction of an enzyme. Thus, several enzymes, which may be nonhomologous, may be identified by the same E.C. number if they catalyze the same
overall reaction. For example, the enzyme with the trivial name lactate dehydrogenase has the EC number 1.1.1.27, is an oxidoreductase (indicated by the first digit)
with the alcohol group of the lactate molecule as the hydrogen donor (second digit)
and NAD+ as the hydrogen acceptor (third digit), and is the 27th enzyme to be categorized within this group (fourth digit). The basic E.C. number classification layout of enzymes is described in Table 1.
The EC classification is still made on the basis of main reaction being catalyzed
(Cuesta et al. 2015). Nowadays the assignment of EC numbers to enzyme is a common routine in the functional annotation of proteins and protein-coding genes in
databases such as UniprotKB (UniProt Consortium 2013) and Ensembl (Kersey
et al. 2014) and has been adopted by the widely uses Gene Ontology (GO)
(Ashburner et al. 2000). However possible changes between EC classes are observed.
There are some preferences such as transferases (EC 2) becoming oxidoreductases
(EC 1), hydrolases (EC 3) and lyases (EC 4) (Martınez Cuesta et al. 2014).
Exchanges between different EC classes suggest that the chemistry of enzymes is
more complex than previously classified with close relationships between enzymes
with radically different EC numbers. The substrate specificity of enzyme is represented by the last digit of the EC number, while the first three digits describe the
type of the reaction. In case the sequence identity is below 70%, all the four digits
of the EC number start to diverge quickly (Rost 2002). This creates an urgent need
to choose alternative methods to sub-group enzymes that reflects their function or
substrate specificity. The chemistry of related enzyme functions can now be explored
using robust computational approaches like EC-BLAST (Rahman et al. 2014). This
tool searches and compares reactions on the basis of bond charges, reaction centers,
and structures of substrates and products (Cuesta et al. 2015; Rausch et al. 2005).
Proteins as Enzymes