Serine hydrolase
Encyclopedia
The serine hydrolase superfamily is one of the largest known enzyme families comprising approximately ~200 enzymes or 1% of the genes in the human proteome. A characteristic defining feature of this superfamily is the presence of an active site
nucleophilic serine
that is used for the hydrolysis
of substrates
. Catalysis
proceeds by the formation of an acyl-enzyme intermediate through this serine, followed by water/hydroxide-induced saponification
of the intermediate and regeneration of the enzyme. Unlike other non-catalytic serines, the nucleophilic serine of these hydrolases is typically activated by a proton relay involving an acidic residue (e.g. aspartate or glutamate) and a basic residue (usually histidine
) although variations on this mechanism exist.
This family includes:
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
nucleophilic serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
that is used for the hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
of substrates
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
. Catalysis
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
proceeds by the formation of an acyl-enzyme intermediate through this serine, followed by water/hydroxide-induced saponification
Saponification
Saponification is a process that produces soap, usually from fats and lye. In technical terms, saponification involves base hydrolysis of triglycerides, which are esters of fatty acids, to form the sodium salt of a carboxylate. In addition to soap, such traditional saponification processes...
of the intermediate and regeneration of the enzyme. Unlike other non-catalytic serines, the nucleophilic serine of these hydrolases is typically activated by a proton relay involving an acidic residue (e.g. aspartate or glutamate) and a basic residue (usually histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
) although variations on this mechanism exist.
This family includes:
- serine proteaseSerine proteaseSerine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
s, including trypsinTrypsinTrypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when...
, chymotrypsinChymotrypsinChymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a...
, and subtilisinSubtilisinSubtilisin is a non-specific protease initially obtained from Bacillus subtilis.Subtilisins belong to subtilases, a group of serine proteases that initiate the nucleophilic attack on the peptide bond through a serine residue at the active site. They are physically and chemically... - Extracellular lipaseLipaseA lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
s, including pancreatic lipasePancreatic lipasePancreatic lipase, also known as pancreatic triacylglycerol lipase, is secreted from the pancreas, and is the primary lipase that hydrolyzes dietary fat molecules in the human digestive system, converting triglyceride substrates found in ingested oils to monoglycerides and free fatty acids.Bile...
, hepatic lipaseHepatic lipaseHepatic lipase is a form of lipase. It is expressed in the liver and adrenal glands.One of the principal functions of hepatic lipase is to convert IDL to LDL.-Clinical significance:...
, gastric lipaseGastric lipaseGastric lipase, also known as LIPF, is an enzymatic protein that, in humans, is encoded by the LIPF gene.-Function:Gastric lipase is an acidic lipase secreted by the gastric chief cells in the fundic mucosa in the stomach. It has a pH optimum of 3-6. Gastric lipase, together with lingual lipase,...
, endothelial lipaseEndothelial lipaseEndothelial lipase is a form of lipase secreted by the endothelial cells.It was first characterized in 1999....
, and lipoprotein lipaseLipoprotein lipaseLipoprotein lipase is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins , into two free... - Intracellular lipaseLipaseA lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
s, including hormone sensitive lipase, monoacylglycerol lipaseMonoacylglycerol lipaseMonoacylglycerol lipase, also known as MAG lipase, MAGL, MGL or MGLL is a protein that, in humans, is encoded by the MGLL gene. MAGL is a 33-kDa, membrane-associated member of the serine hydrolase superfamily and contains the classical GXSXG consensus sequence common to most serine hydrolases...
, adipose triglyceride lipasePNPLA2Patatin-like phospholipase domain-containing protein 2 is an enzyme that in humans is encoded by the PNPLA2 gene.-Further reading:...
, and diacylglycerol lipaseDiacylglycerol lipaseDiacylglycerol lipase, also known as DAG lipase, DAGL or DGL, is a key enzyme in the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. It catalyzes the hydrolysis of diacylglycerol, releasing a free fatty acid and monoacylglycerol.... - CholinesteraseCholinesteraseIn biochemistry, cholinesterase is a family of enzymes that catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.-Types:...
s, including acetylcholinesteraseAcetylcholinesterase"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...
and butyrylcholinesteraseButyrylcholinesteraseButyrylcholinesterase is a non-specific cholinesterase enzyme that hydrolyses many different choline esters... - Small molecule thioesteraseThioesteraseThioesterases are enzymes which belong to the Esterase family. Esterases, in turn, are one type of the several hydrolases known.Thioesterases exhibit Esterase activity specifically at a thiol group.Thioesterases or thiolester hydrolases are identified as members of E.C.3.1.2.-Examples:Acetyl-coA...
s, including fatty acid synthaseFatty acid synthaseFatty acid synthase is an enzyme that in humans is encoded by the FASN gene.Fatty acid synthase is a multi-enzyme protein that catalyzes fatty acid synthesis...
and the acyl-CoA thioesteraseACOT2Acyl-CoA thioesterase 2, also known as ACOT2, is an enzyme which in humans is encoded by the ACOT2 gene.Acyl-CoA thioesterases, such as ACOT2, are a group of enzymes that hydrolyze Coenzyme A esters, such as acyl-CoAs, bile CoAs, and CoA esters of prostaglandins, to the corresponding free acid and...
s - Some phospholipasePhospholipaseA phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
s, including phospholipase A2 and platelet activating factor acetylhydrolase - ProteinProteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
and glycan hydrolases, including protein phosphate methylesterase 1, acyloxyacyl hydrolaseAcyloxyacyl hydrolaseIn enzymology, an acyloxyacyl hydrolase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, the 3-acyl groups of bacterial lipopolysaccharides, and two products, [partially deacylated lipopolysaccharide] and fatty acid.The enzyme removes from lipid A the...
and sialic acid acetylesteraseSialic acid acetylesteraseSialic acid acetylesterase is a enzyme that produces 9-O acetylated sialic acid eg in mammals. It down-regulates B lymphocyte antigen receptor signaling , and is required for immunological tolerance eg in mice.... - Some amidaseAmidaseIn enzymology, an amidase is an enzyme that catalyzes the hydrolysis of an amide:Thus, the two substrates of this enzyme are monocarboxylic acid amide and H2O, whereas its two products are monocarboxylate and NH3....
s, including fatty acid amide hydrolase - Some peptidases, including dipeptiyl peptidase 4, fibroblast activation protein, and prolylendopeptidaseProlyl endopeptidaseProlyl endopeptidase or prolyl oligopeptidase, sometimes post-proline cleaving enzyme) is a large cytosolic enzyme that belongs to a distinct class of serine peptidases. It was first described in the cytosol of rabbit brain as an oligopeptidase, which degrades the nonapeptide bradykinin at the...
See also
- EnzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
- List of enzymes
- EsterEsterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
- AmideAmideIn chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
- ThioesterThioesterThioesters are compounds with the functional group C-S-CO-C. They are the product of esterification between a carboxylic acid and a thiol. Thioesters are widespread in biochemistry, the best-known derivative being acetyl-CoA.-Synthesis:...
- Activity based proteomicsActivity based proteomicsActivity based proteomics, or activity based protein profiling is a functional proteomic technology that uses specially designed chemical probes that react with mechanistically-related classes of enzymes. The basic unit of ABPP is the probe which typically consists of two elements: a reactive...
- Alpha/beta hydrolase foldAlpha/beta hydrolase foldIn molecular biology, the alpha/beta hydrolase fold is common to a number of hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is an alpha/beta-sheet , containing 8 strands connected byhelices...