Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drosophila gliotactin (Gli) is a 109-kDa transmembrane, cholinesterase-like adhesion molecule (CLAM), expressed in peripheral glia, that is crucial for formation of the blood-nerve barrier. The intracellular portion (Gli-cyt) was cloned and expressed in the cytosolic fraction of Escherichia coli BLR(DE3) at 45 mg/L and purified by Ni-NTA (nitrilotriacetic acid) chromatography. Although migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), under denaturing conditions, was unusually slow, molecular weight determination by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) confirmed that the product was consistent with its theoretical size. Gel filtration chromatography yielded an anomalously large Stokes radius, suggesting a fully unfolded conformation. Circular dichroism (CD) spectroscopy demonstrated that Gli-cyt was >50% unfolded, further suggesting a nonglobular conformation. Finally, 1D-(1)H NMR conclusively demonstrated that Gli-cyt possesses an extended unfolded structure. In addition, Gli-cyt was shown to possess charge and hydrophobic properties characteristic of natively unfolded proteins (i.e., proteins that, when purified, are intrinsically disordered under physiologic conditions in vitro).
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PMID:The intracellular domain of the Drosophila cholinesterase-like neural adhesion protein, gliotactin, is natively unfolded. 1457 66

Accumulating evidence supports the view that acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) can influence the proliferation and differentiation of nerve cells. AChE in particular has been found to promote neurite outgrowth in a variety of model systems, possibly by serving as an adhesion molecule. Thus one might suspect that cholinesterase inhibitors would disturb neuronal development, with long-term implications for structure and function in the central and peripheral nervous systems. The actual picture is more complex because AChE's effects on neurite outgrowth may reflect protein-protein interactions that are not directly related to catalytic function but are nonetheless influenced by ligands with special structural features. The putative structural interactions have not yet been rigorously defined, but they are likely to involve enzyme regions at or near the peripheral anionic site. In addition to such effects, some organophosphorus anticholinesterases have been reported to act by still other mechanisms to depress macromolecule synthesis and cell survival in the developing brain. Taken together, this emerging information highlights the potential importance of anticholinesterase agents in developmental neurotoxicology.
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PMID:Can cholinesterase inhibitors affect neural development? 2178 8