Pseudoenzymes are variants of
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s that are catalytically-deficient (usually inactive), meaning that they perform little or no
enzyme catalysis
Enzyme catalysis is the increase in the rate of a process by an "enzyme", a biological molecule. Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs at a localized site, calle ...
. They are believed to be represented in all major
enzyme families in the
kingdoms of life, where they have important signaling and metabolic functions, many of which are only now coming to light. Pseudoenzymes are becoming increasingly important to analyse, especially as the
bioinformatic analysis of
genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
s reveals their ubiquity. Their important regulatory and sometimes disease-associated functions in metabolic and
signalling pathways are also shedding new light on the non-catalytic functions of active enzymes, of moonlighting proteins, the re-purposing of proteins in distinct cellular roles (
Protein moonlighting). They are also suggesting new ways to target and interpret cellular signalling mechanisms using
small molecule
In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; ...
s and drugs. The most intensively analyzed, and certainly the best understood pseudoenzymes in terms of cellular signalling functions are probably the
pseudokinases, the pseudoproteases and the pseudophosphatases. Recently, the pseudo-deubiquitylases have also begun to gain prominence.
Structures and roles
The difference between enzymatically active and inactive
homologues has been noted (and in some cases, understood when comparing catalytically active and inactive proteins residing in recognisable families) for some time at the sequence level, owing to the absence of key catalytic residues. Some pseudoenzymes have also been referred to as 'prozymes' when they were analysed in
protozoan parasites. The best studied pseudoenzymes reside amongst various key signalling superfamilies of enzymes, such as the
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
s, the
protein kinase
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them ( phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a f ...
s, protein phosphatases and
ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...
modifying enzymes. The role of pseudoenzymes as "pseudo scaffolds" has also been recognised and pseudoenzymes are now beginning to be more thoroughly studied in terms of their biology and function, in large part because they are also interesting potential targets (or anti-targets) for drug design in the context of intracellular cellular signalling complexes.
Examples classes
See also
*
Kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
*
Pseudokinase
*
Phosphatome
The phosphatome of an organism is the set of phosphatase genes in its genome. Phosphatases are enzymes that catalyze the removal of phosphate from biomolecules. Over half of all cellular proteins are modified by phosphorylation which typically con ...
*
Protein phosphatase
References
External links
* {{cite web, url=https://www.liverpool.ac.uk/integrative-biology/staff/patrick-eyers/ , title=Patrick Eyers - University of Liverpool , website=Liverpool.ac.uk , date= , access-date=2017-01-16
Biochemistry
Cell signaling
Cancer