Enzymes are essential for many biological processes. Without them, common
tasks such as digesting food or replicating DNA would not be possible.
In recent years, and in part triggered by the expansion of the analysis
and annotation of complete genomes, it has become apparent that several enzyme
families in a wide range of species contain members that look like enzymes but
fail to behave like enzymes. For example, in human, several of these families
have between 5 to 10% of these enzyme-like proteins. Whilst these
proteins have sequences and 3D structure features similar to active enzymes,
they tend to lack essential amino acid residues such as those involved in
catalytic reactions and/or binding substrates, making them incapable of
catalysing chemical reactions. Based on these characteristics, scientists decided
to call them pseudoenzymes.
Why are genes coding for pseudoenzymes maintained in the genome? It turns
out that, despite their lack of enzymatic activity, this group of proteins carries
out essential functions in cells. For example, they help assemble signalling
cascades by acting as scaffolds, they regulate the activity of other enzymes and
ensure that proteins are localized to the right cellular compartment. Consequently,
they have become potential targets for the design of therapeutic
treatments.
To support the growing interest in pseudoenzyme biology, UniProt
recently revisited this important group of proteins. In collaboration with the pseudoenzyme community, we implemented changes
to enhance their identification and discoverability.
The outcome of this project was published in two articles in Science signalling and FEBS journal .
Ultimately, this effort will provide the scientific community with
a comprehensive resource for pseudoenzymes, which in turn will lead to a better
understanding of the evolution of these molecules and their active counterparts
and the aetiology of related diseases. It will also support the ongoing quest
to target pseudoenzymes for therapeutic treatments and offer some insight into
the expanding field of enzyme engineering.
