Serine esterase

Ferri, S. R., and Meighen, E. A. (1991). A Lux-specific myristoyl transferase in luminescent bacteria related to eukaryotic serine esterases. J. Biol. Chem. 266 12852-12857. 

Munger JS, Shi GP, Mark EA, Chin DT, Gerard C, Chapman HA (1991) A serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases. J Biol Chem 266 18832-18838... 

Acetylcholine is a relatively small molecule that is responsible for nerve-impulse transmission in animals. As soon as it has interacted with its receptor and triggered the nerve response, it must be degraded and released before any further interaction at the receptor is possible. Degradation is achieved by hydrolysis to acetate and choline by the action of the enzyme acetylcholinesterase, which is located in the synaptic cleft. Acetylcholinesterase is a serine esterase that has a mechanism similar to that of chymotrypsin (see Box 13.5). 

A potent irreversible inhibitor (abbreviated DFP) of many serine proteinases and serine esterases (especially acetylcholinesterase). This substance is EXTREMELY POISONOUS, but the vapor state can be minimized by using dry, water-miscible solvents such as 2-propanoL. Aqueous solutions become inactivated by hydrolysis, but solutions made with dry 2-propanol are stable at -20°C for many months. 

A sutfonylating agent (abbreviated PMSE) that irreversibly inhibits many serine esterases and serine proteases . Target enzymes usually react with PMSE and related alkylating agents through the activated imidazole group of a histidyl residue that is part of the catalytic triad. 

SERINE DEHYDRATASE SERINE DEHYDRATASE SERINE DEHYDROGENASE Serine esterase inhibitor, irreversible, PHENYLMETHYLSULFONYL FLUORIDE SERINE HYDROXYMETHYLTRANSFERASE SERINE PALMITOYLTRANSFERASE Serine protease inhibitor, irreversible, PHENYLMETHYLSULFONYL FLUORIDE Serine proteinase inhibitor,... 

In addition to cutinases, various lipases, such as from C. antarctica, Candida sp. [13, 47], Thermomyces lanuginosus [2, 14, 15, 55, 56], Burkholderia (formerly Pseudomonas) cepacia [57] and esterases from Pseudomonas sp. (serine esterase) [58] and Bacillus sp. (nitrobenzyl esterases) [59, 60], have shown PET hydrolase... 

The first examples of mechanism must be divided into two principal classes the chemistry of enzymes that require coenzymes, and that of enzymes without cofactors. The first class includes the enzymes of amino-acid metabolism that use pyridoxal phosphate, the oxidation-reduction enzymes that require nicotinamide adenine dinucleotides for activity, and enzymes that require thiamin or biotin. The second class includes the serine esterases and peptidases, some enzymes of sugar metabolism, enzymes that function by way of enamines as intermediates, and ribonuclease. An understanding of the mechanisms for all of these was well underway, although not completed, before 1963. 

The mechanism of action of anticholinesterases is to form a stable covalent complex with the Achase enzyme. Achase is one of several enzymes known as serine esterases. Other examples include the intestinal enzymes trypsin and chymotrypsin as well as the blood clotting agent thrombin. During the course of the catalysis the alcohol -OH of a serine side chain in the active site of the enzyme forms an ester complex, called the acyl-enzyme, with the substrate. So, acetylcholine will go through similar chemical reactions with Achase. 

Farm workers are especially susceptible to organophosphate insecticide poisoning. Unsafe spraying conditions can lead to accumulated toxicity and chronic symptoms. Since there are many enzymes in the body which are in the serine esterase family along with Achase and can complex... 

All of these drugs are metabolized by serine esterases. It should be noted, however, that babies cannot perform such hydrolysis reactions as readily and the materials will remain in the blood stream for four days. 

GXSXG lipase consensus sequence 8 an-kyrin repeats Ca2+-in-dependent catalytic activity, proline-rich consensus motif (PX5PX8HHPX12NX4Q), LH-iPLA 2 (long isoform, 88 kDa) but not SH-iPLA2 (short isoform, 85 kDa) is activated by ATP GDSXV modified consensus sequence of serine esterase family catalytic triad Ser-His-Asp P and y subunits form a heter-otrimer with a 45-kDa noncatalytic subunit Ca2+-indepen-dent catalytic activity 0 Ca2+-independent catalytic activity... 

Like pancreatic lipase, this enzyme is clearly dependent on a lipid/water interface for maximal activity, where it also may reach a very high catalytic rale, Abo like pancreatic lipase, it is not inhibited by serine esterase inhibitors like DFP orPMSF. 

Acetylcholinesterase (AChE) deesterifies the neurotransmitter acetylcholine (ACh). AChE belongs to a group of enzymes considered serine esterases and has a mechanism similar to that of chymotrypsin. AChE has an anionic binding site that attracts the positively charged quaternary ammonium group of ACh. The serine then attacks and cleaves the ester.910... 

During inflammation, degranulation of immune cells releases serine proteases that pass through and bind to the capillary wall. Increased levels of Bik suppress these immune cell proteases and protect the extracellular matrix in arterial walls and connective tissue [4]. Bik inhibits phagocytic destruction of cells. Bik has been shown to inhibit elastases, granzymes A and K [4, 57], Mast cell tryptases (J3- and a-tetrameric forms with a molecular weight of 134 kDa) are resistant to aprotinin [58]. Lymphocytes serine esterase TL2 is not inhibited by Bik [59]. 

A good example of this is the classic work by Bender (6) on the reaction ofra-f-butylphenyl acetate. This substrate binds well into the cavity, and the substrate then undergoes an acetyl transfer reaction in which a cyclodextrin hydroxyl group is acetylated. The reaction can be compared with the first step in the action of a serine esterase, or a serine protease acting on an ester substrate. However, the acceleration of this acetyl transfer, compared with simple hydrolysis by the medium, was only 250-fold. 

According to this model, the action of the peptide catalysts used in the Julid-Colonna epoxidation bears a lot of similarity to that of enzymes, in particular the binding/activation and proper orientation of the substrates which ultimately effects the excellent enantioselectiv-ities in the overall process. In fact, the H-bonding motif discovered as the catalytically active site also acts as the oxy-anion hole in serine esterases and is known to bind/stabilize a variety of fully or partially negatively charged entities (Milner-White and Watson 2002a,b), the P-hydroperoxyenolate, in the present case. Studies by Roberts, Kelly,... 

Cutinases are hydrolytic serine esterases that degrade cntin, a polyester of hydroxy and epoxy fatty acids (Purdy and Kolattukudy, 1975) and specific for primary alcohol esters (Murphy et al., 1996). The fatty acids of cutin are usually n-C16 and -C18 oxygenated hydroxyacids (containing one to three hydroxyl gronps). Cntins are lipid-based polymers of plants and ester bonds dominate in the cutins. Therefore, cntinases... 

It must be pointed out, however, that the catalytic role ( yed by the imidazole group at the active site of serine esterases is different frimi that of Eq. (4—1). The imidazole group at the active ate helps acyiatifH) and deaQdation at the seiyl 1 -droxyl group as general base (see Fig. 2—1), whereas in Eq. (4—1) imidazde acts as a nucleophilic catalyst. 

Walday, P., Aas, P., Fonniun, F. (1991). Inhibition of serine esterases in different rat tissues following inhalation of soman. Biochem. Pharmacol. 41 151-3. 

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