pseudoenzymes
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Pseudoenzymes are variants of
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s (usually
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s) that are catalytically-deficient (usually inactive), meaning that they perform little or no
enzyme catalysis Enzyme catalysis is the increase in the reaction rate, rate of a process by a Biomolecule, biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs ...
. 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 Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combine ...
analysis of
genome In the fields of molecular biology and genetics, 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 g ...
s reveals their ubiquity. Their important regulatory and sometimes disease-associated functions in metabolic and
signalling pathway In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
s 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 Protein moonlighting (or gene sharing) is a phenomenon by which a protein can perform more than one function. Ancestral moonlighting proteins originally possessed a single function but through evolution, acquired additional functions. Many prote ...
). They are also suggesting new ways to target and interpret cellular signalling mechanisms using
small molecule Within the fields of 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 ...
s and drugs. The most intensively analyzed, and certainly the best understood pseudoenzymes in terms of cellular signalling functions are probably the
pseudokinase Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life. Pseudokinases have both physiological (signal transduction) and pathophysiological functions. Hist ...
s, 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, and some pseudoenzymes have also been referred to as 'prozymes' when they were analysed in
protozoan parasite Protozoan infections are parasitic diseases caused by organisms formerly classified in the kingdom Protozoa. They are usually contracted by either an insect vector or by contact with an infected substance or surface and include organisms that are ...
s. 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 catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
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 fu ...
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 1980s. Fo ...
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 *
Pseudokinase Pseudokinases are catalytically-deficient pseudoenzyme variants of protein kinases that are represented in all kinomes across the kingdoms of life. Pseudokinases have both physiological (signal transduction) and pathophysiological functions. Hist ...
*
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 cont ...
*
Protein phosphatase A protein phosphatase is a phosphatase enzyme that removes a phosphate group from the phosphorylated amino acid residue of its substrate protein. Protein phosphorylation is one of the most common forms of reversible protein posttranslational modif ...


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