Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the active site residue, human milk bile-salt stimulated lipase (BSSL) was labelled with [3H]diisopropyl fluorophosphate (DFP). Partial sequence analysis of cyanogen bromide fragments (a total of 146 residues from 6 peptides) revealed 84% sequence identity with a putative rat lysophospholipase. Sequence analysis of a [3H]DFP-labelled peptide indicated that the active site serine was contained in the sequence Gly-Glu-Ser-Ala-Gly. In addition to similarity with rat lysophospholipase, this sequence showed homology with regions of human butyrylcholinesterase and electric ray acetylcholinesterase (68% identity). It is concluded that these proteins are members of a new supergene family.
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PMID:Human milk bile-salt stimulated lipase. Sequence similarity with rat lysophospholipase and homology with the active site region of cholinesterases. 199 11

Developing cells of Dictyostelium discoideum contain crystalline inclusion bodies. The interlattice spaces of the crystals are approximately 11 nm, and their edge dimensions vary in aggregating cells from 0.1 to 0.5 micron. The crystals are enclosed by a membrane with the characteristics of RER. To unravel the nature of the crystals we isolated them under electron microscopical control and purified the two major proteins that cofractionate with the crystals, one of an apparent molecular mass of 69 kD, the other of 56 kD. This latter protein proved to be identical with the protein encoded by the developmentally regulated D2 gene of D. discoideum, as shown by its reactivity with antibodies raised against the bacterially expressed product of a D2 fusion gene. The D2 gene is known to be strictly regulated at the transcript level and to be controlled by cAMP signals. Accordingly, very little of the 56-kD protein was detected in growth phase cells, maximal expression was observed at the aggregation stage, and the expression was stimulated by cAMP pulses. The 69-kD protein is the major constituent of the crystals and is therefore called "crystal protein." This protein is developmentally regulated and accumulates in aggregating cells similar to the D2 protein, but is not, or is only slightly regulated by cAMP pulses. mAbs specific for either the crystal protein or the D2 protein, labeled the intracellular crystals as demonstrated by the use of immunoelectron microscopy. The complete cDNA-derived amino acid sequence of the crystal protein indicates a hydrophobic leader and shows a high degree of sequence similarity with Torpedo acetylcholinesterase and rat lysophospholipase. Because the D2 protein also shows sequence similarities with various esterases, the vesicles filled with crystals of these proteins are named esterosomes.
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PMID:Membrane-enclosed crystals in Dictyostelium discoideum cells, consisting of developmentally regulated proteins with sequence similarities to known esterases. 230 2

About 30% of the primary structure of acetylcholinesterase (AchE) from the cobra Naja naja oxiana has been determined. The sequence around the serine residue labeled by diisopropylfluorophosphate (DFP) was found to be TVTLFGESAGAASVGM which is similar to the active sites of AChE from other tissues. The part of the primary structure determined shows 76% identity with AChE from Torpedo and 42% identity with the Drosophila enzyme. A surprisingly large identity (42% in the sequence determined) was found with lysophospholipase from rat.
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PMID:The active site and partial sequence of cobra venom acetylcholinesterase. 234 76

The complete amino acid sequence of a mammalian acetylcholinesterase from fetal bovine serum (FBS AChE) is presented. This enzyme has a high degree of sequence identity with other cholinesterases, liver carboxyesterases, esterase-6, lysophospholipase, and thyroglobulin. The locations of 191 amino acids in 10 regions of the FBS enzyme were compared with corresponding sequences of Torpedo, human, and Drosophila AChEs and human serum butyrylcholinesterase (BChE). In one region there is a marked difference in both the number of amino acids and their sequence between mammalian AChE and other AChEs and the human serum BChE. The amino acid sequence of FBS AChE showed overall homologies of 90% with human AChE, 60% with T. california AChE, 50% with human serum BChE, and 39% with Drosophila AChE in these regions.
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PMID:Complete amino acid sequence of fetal bovine serum acetylcholinesterase and its comparison in various regions with other cholinesterases. 236 60

Potent cannabinoid CB1 receptor ligands include anandamide [N-(2-hydroxyethyl)arachidonamide], Delta9-tetrahydrocannabinol, and 3H-CP 55,940 at the agonist site and selected organophosphorus esters (including some pesticides) and organosulfur compounds at a proposed closely coupled "nucleophilic" site. This study considers the toxicological and structural features of alkylfluorophosphonates, benzodioxaphosphorin oxides, alkanesulfonyl fluorides, and analogs acting at the nucleophilic site. Binding at the agonist site, using3H-CP 55,940 in assays with mouse brain membranes, is inhibited byO-isopropyl dodecylfluorophosphonate (compound 2), dodecanesulfonyl fluoride (compound 14) and dodecylbenzodioxaphosphorin oxide with IC50 values of 2-11 nM. Compounds 2 and 14 are also effectivein vivo, with 84% inhibition of mouse brain CB1 binding 4 h after intraperitoneal dosage at 30 mg/kg. Compound 14-inhibited CB1 in mouse brain requires about 3-4 days for recovery of 50% activity, suggesting covalent derivatization. Delayed toxicity (mortality in 0.3-5 days) from compounds 2, 14, and octanesulfonyl fluoride (18) is more closely associated with in vivo inhibition of brain neuropathy target esterase-lysophospholipase (NTE-LysoPLA) than with that of CB1 or acetylcholinesterase. NTE-LysoPLA inhibited by sulfonyl fluorides 14 and 18 cannot "age," a proposed requirement for NTE phosphorylated by organophosphorus-delayed neurotoxicants. Several octane- and dodecanesulfonamides with N-(2-hydroxyethyl) and other substituents based on anandamide give depressed mobility and recumbent posture in mice, but the effects do not correlate with potency for CB1 inhibition in vitro. Specific toxicological responses are not clearly associated with organophosphorus- or organosulfur-induced inhibition of the proposed CB1 nucleophilic site in mouse brain. On the other hand, the most potent CB1 inhibitors examined here are also NTE-LysoPLA inhibitors and cause delayed toxicity in mice.
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PMID:Toxicological and structural features of organophosphorus and organosulfur cannabinoid CB1 receptor ligands. 1294 86