What’s an EC Number & how to interpret it

You might have heard about EC numbers.

They are widely used in biochemistry and molecular biology to provide a clear and standardized way to refer to enzymes, especially in scientific literature and databases.

This classification method helps us differentiate among thousands of enzyme types that, otherwise, would be very hard to recognise by everyone.

Because giving enzymes arbitrary, common names worked well when only a few were known.

But now, after more than a century of enzyme discovery, naming more than 8.000 enzymes would be simply impossible.

Only a few names have survived in our common language, such as cellulase (EC 3.2.1.4), papain (EC 3.4.22.2) or proteases (all EC 3.4. numbers). For the rest, EC numbers are our only and best way to talk about the broad world of biocatalysis.

What’s an EC Number?

The Enzyme Commission (EC) number is a nomenclature system based on the chemical reactions that these proteins catalyze.

It was developed by the International Union of Biochemistry and Molecular Biology (IUBMB) and consists of a numerical classification scheme where each number is associated with an enzyme-catalyzed reaction.

Note that each EC number is not associated with a specific enzyme, because in nature we can find different enzymes that catalyze the same reaction.

How to read an EC number

An EC number is typically represented as a sequence of four numbers separated by periods, which is linked to a recommended name. For example, EC 1.1.1.1 (alcohol dehydrogenase).

Let’s see what each of these four numbers represents:

First Number: The type of reaction or enzyme class

The first number indicates the enzyme class, based on the type of reaction each of these classes catalyzes. There are seven main classes:

• • EC 1: Oxidoreductases - Enzymes that catalyze oxidation-reduction reactions.
  • EC 2: Transferases - Enzymes that transfer a functional group (e.g., a methyl or phosphate group).
  • EC 3: Hydrolases - Enzymes that catalyze the hydrolysis of various bonds.
  • EC 4: Lyases - Enzymes that break various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or ring structure.
  • EC 5: Isomerases - Enzymes that catalyze the transfer of groups within molecules to yield isomeric forms.
  • EC 6: Ligases - Enzymes that join two molecules together, typically using ATP.
  • EC 7: Translocases - Enzymes that catalyze the movement of ions or molecules across membranes or their separation within membranes.

Second and third numbers: Enzyme subclass and sub-subclass

These two numbers provide more detail about the type of molecular group, bond or product involved in the enzyme-catalyzed reaction, narrowing down the specificity of the reaction.

Fourth Number: Enzyme identification

This is the serial number of the enzyme. It represents the specific enzyme identity, related to specific metabolites and/or cofactors involved in the enzyme-catalyzed reaction.

A couple of examples

Now that you know the basics, let’s see how this looks put into practice.

Let’s start with the first number that appears in the classification:

EC 1.1.1.1

• • The first "1" indicates that it's an oxidoreductase (an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, to another, the oxidant).
  • The second "1" specifies that it acts on the CH-OH group of donors.
  • The third "1" indicates that NAD+ or NADP+ is the acceptor.
  • The final "1" is the specific serial number for this enzyme in its group, which is given the recommended name of alcohol dehydrogenase.

See? That wasn’t so hard. Now let’s mix it up a little and look at another one.

EC 6.3.2.24

• • Here, the first "6" indicates that it's a ligase (an enzyme that catalyzes the joining of two molecules by forming a new chemical bond).
  • The second number is "3" and specifies that the type of bonds that forms are carbon-nitrogen.
  • The third number is "2" and specifies that the types of molecules that are bonded are an acid and an amino-acid.
  • The last number is "24", the specific serial number for this enzyme in its group, and specifies that the two amino acids bond catalyzed by the enzyme is tyrosine—arginine, which gives the recommended name of tyrosine—arginine ligase.

Are you starting to get the hang of it? This classification is quite easy to follow. And, don’t worry, nobody expects you to know all these numbers by heart. You just need to understand the rationale behind. After all, EC numbers are here to make our lives easier!

Is there a complete enzyme classification by EC number?

Of course! People have always loved to bring order to chaos.

In this case, it is the IUBMB who provides an approved and updated enzyme classification list based on the EC number nomenclature: the ExplorEnz Enzyme Database.

The first edition was published in 1992. From then on, 29 more supplements or edits have been added to that initial version to register all the new enzymes discovered and modifications needed.

You can dive into its tree structure, expanding each list of the classes, subclasses, sub-subclasses and serial numbers, to have a deeper view of the entire classification.

How to find the enzyme that I’m searching for?

If you’ve ever had to find out if a certain reaction can be performed enzymatically, you may know the answer does not come easily navigating through the EC numbers database on your own.

This is a very common problem for industries or research groups considering the possibility of doing a chemical process with enzymes, who usually spend too much time searching in the literature or asking other colleagues.

In those cases, a quick and simple answer in the form of an EC number can save a lot of time and open the door to innovative projects that were long stuck.

At ZYMVOL we developed ZYMSCAN with that in mind: if a chemist wants to know if their reaction can be done enzymatically, they just have to submit their reaction and ZYMSCAN will confirm if it can be done with biocatalysis. In case it can, they will receive an email with the EC number of the enzyme family that matches the reaction.

As you can see, an EC number can be very useful not only in scientific literature, but also in applied chemistry; and now you know how to interpret it!