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Electron paramagnetic resonance reveals altered topography of the active center gorge of acetylcholinesterase after binding of fasciculin to the peripheral siteŠentjurc, Marjeta ...Fasciculin, a peptidic toxin from snake venom, inhibits mammalian and fish acetylcholynesterases (AChE) by binding to the peripherial site of the enzyme.This site is located at the rim of a narrow, ... deep gorge which leads to the active center traid, located at its base. The proposed mechanisms for AChE inhibitions by fasciculin include allosteric events resulting in alterde conformation of the AChE active center gorge. However, a fasciculin-induced altered topography of the active center gorge has not been directly demonstrated. Using electron paramagnetic resonance with the spin-labeled organophosphate 1-oxyl-2,26,6-tetramethyl-4-piperidinylphosphorofluoridate (EtOSL) specificaly bound to the catalytic serine of mouse AChE (mACHE), we show that bound fasciculin on mAChE slows down, but does not prevent phopshorylation of the active site serine by EtOSL and protests the gorge conformation against thermal denaturation. Most importantly, a restricted freedom of motion of the spin label bound to the fasciculin-associated mAChE, compared to mAChE, is evidenced. Molecular models of mAChE and fasciculin-associated mAChE with tethered EtOSL enantiomers indicate that this restricted motion is due to greater proximity of the S-EtOSL nitroxide radical to the W86 residue in the fasciculin-associated enzyme. Our results demonstrate a topographical alteration indicative of a restricted conformation of the active center gorge of mAChE with bound fasciculin at its rim.Vir: Biochimica et biophysica acta. Protein structure and molecular enzymology. - ISSN 0167-4838 (Vol. 1429, 1999, str. 349-358)Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasleLeto - 1999Jezik - angleškiCOBISS.SI-ID - 484465
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vir: Biochimica et biophysica acta. Protein structure and molecular enzymology. - ISSN 0167-4838 (Vol. 1429, 1999, str. 349-358)
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Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Šentjurc, Marjeta | 01119 |
Pečar, Slavko | 03070 |
Stojan, Jure, 1956- | 03723 |
Grubič, Zoran, 1948- | 04410 |
Vir: Osebne bibliografije
in: SICRIS
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