pKa Calculation for Selected Active Site Residues in Acetylcholinesterase

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

pKa Calculation for Selected Active Site Residues in Acetylcholinesterase

Popis výsledku v původním jazyce

Acetylcholinesterase (AChE) is a vitally important enzyme participating in nerve signal transmission connected with Alzheimer disease and nerve agent poisoning. Molecular dynamics simulations in the Amber force field 03 have revealed large conformationalchanges of the omega loop (Cys69 ? Cys96 in 2HA2 crystal structure) occurring when AChE is in its deprotonated state [1]. According to the ff03 MD results, the omega loop dynamics is dependent of the protonation of active site residues, namely Glu202, Glu334, Glu450 (numbering of 2HA2). Simulations of the protonated AChE show much more stable and less mobile omega loop and Trp86. Such omega loop conformations are not seen in any of the crystal structures of AChE. Furthermore, a great deal of experimental evidence disproves that larger conformational rearrangements of omega loop would take part in the reaction mechanism [2].

Název v anglickém jazyce

pKa Calculation for Selected Active Site Residues in Acetylcholinesterase

Popis výsledku anglicky

Acetylcholinesterase (AChE) is a vitally important enzyme participating in nerve signal transmission connected with Alzheimer disease and nerve agent poisoning. Molecular dynamics simulations in the Amber force field 03 have revealed large conformationalchanges of the omega loop (Cys69 ? Cys96 in 2HA2 crystal structure) occurring when AChE is in its deprotonated state [1]. According to the ff03 MD results, the omega loop dynamics is dependent of the protonation of active site residues, namely Glu202, Glu334, Glu450 (numbering of 2HA2). Simulations of the protonated AChE show much more stable and less mobile omega loop and Trp86. Such omega loop conformations are not seen in any of the crystal structures of AChE. Furthermore, a great deal of experimental evidence disproves that larger conformational rearrangements of omega loop would take part in the reaction mechanism [2].

Druh

O - Ostatní výsledky

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2011

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů