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Etude des relations structure-dynamique-fonction au sein de l`acetylcholinesterase

Jacques-Philippe Colletier 1
1 LBM - Laboratoire de Biophysique Moléculaire
IBS - UMR 5075 - Institut de biologie structurale , CEA - Commissariat à l'énergie atomique et aux énergies alternatives : DSV/IBS
Abstract : Acetylcholinesterase is a very rapid enzyme, essential in the process of nerve impulse transmission at cholinergic synapses. It is the target of all currently approved anti-Alzheimer drugs and further progress in the modulation of its activity requires structural as well as dynamical information. Here we report three experimental approaches that allowed to gain structural insight into the dynamics of acetylcholinesterase. First, the structure of its complex with a putative secondgeneration anti-Alzheimer drug is presented. Next, a steady-state approach for determining atomic-resolution structures of enzyme/substrate complexes is detailed, which permitted to structurally follow the traffic of substrates within the active site of the acetylcholinesterase. Lastly, a new kinetic-crystallography strategy is described, in which UV-laser induced cleavage of a photolabile precursor of the enzymatic product is combined with temperaturecontrolled X-ray crystallography, in order to enable the molecular motions necessary for the expulsion of photolysis products to occur. Taken together, the results described herein permit a detailed description of the traffic of substrates and products within acetylcholinesterase, and provide insights into its conformational energy landscape.
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https://tel.archives-ouvertes.fr/tel-00263679
Contributor : Jacques-Philippe Colletier <>
Submitted on : Wednesday, March 12, 2008 - 10:48:06 PM
Last modification on : Thursday, November 19, 2020 - 1:20:08 PM
Long-term archiving on: : Friday, May 21, 2010 - 12:24:07 AM

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  • HAL Id : tel-00263679, version 1

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Jacques-Philippe Colletier. Etude des relations structure-dynamique-fonction au sein de l`acetylcholinesterase. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2006. Français. ⟨tel-00263679⟩

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