The hydrolases are enzymes that are responsible for hydrolyzing various types of chemical bonds in many different compounds. Among the main bonds that hydrolyze are ester, glycosidic, and peptide bonds.
Within the group of hydrolases, more than 200 different enzymes have been classified, grouped in at least 13 individual sets; their classification is essentially based on the type of chemical compound that serves as their substrate.
Graphic modeling with bioinformatics tools of the structure of a hydrolase (Source: Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute Via Wikimedia Commons)
Hydrolases are essential for the digestion of food in the intestines of animals, since they are responsible for degrading a large part of the bonds that make up the carbonate structures of the food they eat.
These enzymes work in aqueous media, since they need water molecules around them to add to the compounds once the molecules are cleaved. In simple words, hydrolases perform a hydrolytic catalysis of the compounds on which they act.
For example, when a hydrolase breaks a CC covalent bond, the result is usually a C-OH group and a CH group.
Structure
Like many enzymes, hydrolases are globular proteins organized into complex structures that organize themselves through intramolecular interactions.
Hydrolases, like all enzymes, bind to one or more substrate molecules in a region of their structure known as the "active site." This site is a pocket or cleft surrounded by many amino acid residues that facilitate grip or attachment of the substrate.
Each type of hydrolase is specific for a given substrate, which is determined by its tertiary structure and by the conformation of the amino acids that make up its active site. This specificity was raised in a didactic way by Emil Fischer as a kind of "lock and key".
It is now known that the substrate, in general, induces changes or distortions in the conformation of enzymes and that the enzymes, in turn, distort the structure of the substrate to make it "fit" in its active site.
Features
All hydrolases have the main function of breaking chemical bonds between two compounds or within the structure of the same molecule.
There are hydrolases to break almost any type of bond: some degrade the ester bonds between carbohydrates, others the peptide bonds between the amino acids of proteins, others the carboxylic bonds, etc.
The purpose of the hydrolysis of chemical bonds catalyzed by a hydrolase enzyme varies considerably. Lysozyme, for example, is responsible for the hydrolysis of chemical bonds with the purpose of protecting the organism that synthesizes it.
This enzyme breaks down the bonds that hold compounds together in the bacterial cell wall, in order to protect the human body from bacterial proliferation and possible infection.
Nucleases are "phosphatase" enzymes that have the ability to degrade nucleic acids, which can also represent a cellular defense mechanism against DNA or RNA viruses.
Other hydrolases, such as those of the "serine proteases" type, degrade the peptide bonds of proteins in the digestive tract to make amino acids assimilable in the gastrointestinal epithelium.
Hydrolases are even involved in various energy production events in cell metabolism, since phosphatases catalyze the release of phosphate molecules from high-energy substrates such as pyruvate, in glycolysis.
Examples of hydrolases
Among the great diversity of hydrolases that scientists have identified, some have been studied with greater emphasis than others, since they are involved in many processes essential for cell life.
These include lysozyme, serine proteases, endonuclease-type phosphatases, and glucosidases or glycosylases.
Lysozyme
Enzymes of this type break down the peptidoglycan layers of the cell wall of gram-positive bacteria. This usually ends up causing a total lysis of the bacteria.
Lysozymes defend the body of animals from bacterial infections and are abundant in body secretions in tissues that are in contact with the environment, such as tears, saliva and mucus.
The chicken egg lysozyme was the first protein structure that crystallized through X-rays. This crystallization was carried out by David Phillips, in 1965, at the Royal Institute in London.
The active site of this enzyme is composed of the peptide Asparagine-Alanine-Methionine-Asparagine-Alanine-Glycine-Asparagine-Alanine-Methionine (NAM-NAG-NAM).
Serine proteases
The enzymes in this group are responsible for hydrolyzing the peptide bonds in peptides and proteins. The most commonly studied are trypsin and chymotrypsin; however, there are many different types of serine proteases, which vary with respect to substrate specificity and their catalysis mechanism.
The "serine proteases" are characterized by having a nucleophilic amino acid of the serine type in their active site, which functions in the breaking of the peptide bond between amino acids. Serine proteases are also capable of breaking a wide variety of ester bonds.
Graphic scheme of the action of a serine protease breaking a peptide bond in the amino acid histidine (Source: Zephyris at the English language Wikipedia Via Wikimedia Commons)
These enzymes cut peptides and proteins nonspecifically. However, all peptides and proteins to be cut must be attached at the N-terminus of the peptide bond to the active site of the enzyme.
Each serine protease precisely cuts the amide bond that forms between the C-terminal end of the amino acid at the carboxyl end and the amino acid amine that is towards the N-terminal end of the peptide.
Nuclease-type phosphatases
These enzymes catalyze the cleavage of the phosphodiester bonds of the sugars and the phosphates of the nitrogenous bases that make up the nucleotides. There are many different types of these enzymes, as they are specific for the nucleic acid type and the cleavage site.
Graphic scheme of the action of an endonuclease hydrolyzing a phosphodiester bond (Source: J3D3 Via Wikimedia Commons)
Endonucleases are indispensable in the field of biotechnology, since they allow scientists to modify the genomes of organisms by cutting and replacing fragments of the genetic information of almost any cell.
Endonucleases carry out the cleavage of nitrogenous bases in three steps. The first is through a nucleophilic amino acid, then an intermediate structure with a negative charge is formed that attracts the phosphate group and finally breaks the bond between both bases.
References
- Davies, G., & Henrissat, B. (1995). Structures and mechanisms of glycosyl hydrolases. Structure, 3 (9), 853-859.
- Lehninger, AL, Nelson, DL, Cox, MM, & Cox, MM (2005). Lehninger principles of biochemistry. Macmillan.
- Mathews, AP (1936). Principles of biochemistry. W. Wood.
- Murray, RK, Granner, DK, Mayes, P., & Rodwell, V. (2009). Harper's illustrated biochemistry. 28 (p. 588). New York: McGraw-Hill.
- Ollis, DL, Cheah, E., Cygler, M., Dijkstra, B., Frolow, F., Franken, SM,… & Sussman, JL (1992). The α / β hydrolase fold. Protein Engineering, Design and Selection, 5 (3), 197-211.