The key difference between aspartyl cysteine and serine proteases is their functional groups that act as catalytic residues. The functional group that acts as the catalytic residues of aspartyl protease is a carboxylic acid group, while in cysteine protease, a thiol or sulfhydryl group acts as the functional group at the catalytic residue, and in serine protease, a hydroxyl group or an alcohol acts as the functional group at the catalytic residue.
Proteases are enzymes that catalyze proteolysis, which is the breakdown of proteins into smaller polypeptides or amino acids. This process takes place by cleaving peptide bonds within proteins by a hydrolysis process. Proteases are involved in many biological functions, such as digestion of ingested proteins, catabolism of proteins, and cell signaling. Proteases are present in all forms of life. Aspartyl, cysteine, and serine are three important proteases that play a key role in living organisms.
1. Overview and Key Difference
2. What are Aspartyl Proteases
3. What are Cysteine Proteases
4. What are Serine Proteases
5. Similarities – Aspartyl Cysteine and Serine Proteases
6. Aspartyl vs Cysteine vs Serine Proteases in Tabular Form
7. Summary –Aspartyl vs Cysteine vs Serine Proteases
What are Aspartyl Proteases?
Aspartyl proteases are a type of protein-breaking enzymes. They have two highly conserved aspartates in the active site, and they are optimally active at acidic pH. These proteases cleave dipeptide bonds that have hydrophobic residues as well as a beta-methylene group. The catalytic mechanism of aspartyl protease is an acid-base mechanism. This involves the coordination of a water molecule with two aspartate residues. One aspartate activates the water molecule by removing a proton. This enables the water to perform a nucleophilic attack on the carbonyl carbon of the substrate. As a result, it generates a tetrahedral oxyanion intermediate that is stabilized by hydrogen bonds with the second aspartate residue. The rearrangement of this intermediate is responsible for the splitting of the peptide into two peptide products.
There are five superfamilies of aspartic proteases: Clan AA which is a family, Clan AC, which is a signal peptidase II family, Clan AD, which is a presenilin family, Clan AE, which is a GPR endopeptidase family, and Clan AF, which is an omptin family.
What are Cysteine Proteases?
Cysteine proteases are a group of hydrolase enzymes that degrade proteins. They show a catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic triad or dyad. The initial step in the catalytic mechanism of cysteine proteases is deprotonation. The thiol group becomes deprotonated within the active site of the enzyme by an adjacent amino acid such as histidine, which has a basic side chain. The next step is the nucleophilic attack by the deprotonated anionic sulfur of cysteine on the substrate. Here, the fragment of the substrate releases with an amine, and the histidine residue in the protease restores its deprotonated form. This results in the formation of the thioester intermediate of the substrate, linking the new carboxy terminus to the cysteine thiol. The thioester bond hydrolyzes to generate carboxylic acid moiety on the remaining substrate fragment.
Cysteine proteases play multiple roles in physiology and development. In plants, they play an important role in the growth, development, accumulation, and mobilization of storage proteins. In humans, they are important in senescence and apoptosis, immune responses, prohormone processing, and extracellular matrix remodeling to cone development.
What are Serine Proteases?
Serine proteases are also a group of proteolytic enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the active site of the enzyme. These are present in both eukaryotes and prokaryotes. Serine proteases are usually divided into different categories by a distinctive structure that consists of two beta-barrel domains converging at the active catalytic site and also based on their substrate specificity. They are trypsin-like, chymotrypsin-like, thrombin-like, elastase-like, and subtilisin-like.
Trypsin-like proteases cleave peptide bonds following a positively charged amino acid such as lysine or arginine. They are specific to negatively charged residues such as aspartic acid or glutamic acid. Chymotrypsin-like proteases are more hydrophobic. Their specificity lies with large hydrophobic residues such as tyrosine, tryptophan, and phenylalanine. Thrombin-like proteases include thrombin, which is a tissue activating plasminogen, and plasmin. These help in the coagulation of blood and digestion and also in pathophysiology in neurodegenerative disorders. Elastase-like proteases prefer residues such as alanine, glycine, and valine. Subtilisin-like proteases include serine in prokaryotes. It shares a catalytic mechanism utilizing a catalytic triad in order to create a nucleophilic serine. The regulation of the serine protease activity requires an initial protease activation and secretion of inhibitors.
What are the Similarities Between Aspartyl Cysteine and Serine Proteases?
- Aspartyl, cysteine, and serine proteases catalyze the breakdown of proteins by cleavage of peptide bonds.
- Mechanisms are similar where the active site residues attack the peptide bonds causing it to break.
- All contain nucleophiles.
- They all are proteins.
What is the Difference Between Aspartyl Cysteine and Serine Proteases?
The key difference between aspartyl cysteine and serine proteases depends on their functional group, which acts as the catalytic residues. In aspartyl protease, a carboxylic acid group acts as the functional group, while in cysteine protease, a thiol or sulfhydryl group acts as the functional group, and in serine protease, a hydroxyl group or an alcohol acts as the functional group.
Aspartyl proteases have an aspartate active site, while cysteine proteases have a cysteine active site. The active site residue of serine protease is a hydroxyl group. Thus, this is also another difference between aspartyl cysteine and serine proteases. Unlike serine and cysteine proteases, aspartyl proteases do not form a covalent intermediate during the process of cleaving. Therefore, proteolysis occurs in a single step for aspartyl proteases.
The below infographic presents the differences between aspartyl cysteine and serine proteases in tabular form for side by side comparison.
Summary – Aspartyl Cysteine vs Serine Proteases
Proteases are enzymes that catalyze the breakdown of proteins into smaller polypeptides or amino acids. The key difference between aspartyl cysteine and serine proteases is the functional group that acts as their catalytic residue. A carboxylic acid group acts as the functional group in aspartyl protease, while a thiol or sulfhydryl group acts as the functional group in cysteine protease. A hydroxyl group or an alcohol acts as the functional group in serine protease.
1. “Protease Mechanisms.” Scitable, Nature News, Nature Publishing Group.
2. “Cysteine protease.” Science Direct.
3. “Serine protease.” Science Direct.
1. “Aspartyl protease mechanism” By English Wikipedia user Roadnottaken (CC BY-SA 3.0) via Commons Wikimedia
2. “Cysteinprotease Reaktionsmechanismus” By NEUROtiker – Own work (Public Domain) via Commons Wikimedia
3. “Serine protease mechanism by snellios” By Snellios at the English-language Wikipedia (CC BY-SA 3.0) via Commons Wikimedia
Leave a Reply