Tryptophane as a Rotating Flap: Omega Loop Dynamics in Acetylcholinesterase

WIESNER, Jiří, Zdeněk KŘÍŽ and Jaroslav KOČA. Tryptophane as a Rotating Flap: Omega Loop Dynamics in Acetylcholinesterase. In Modeling Interactions in Biomolecules III. 2007.

Basic information

• Original name: Tryptophane as a Rotating Flap: Omega Loop Dynamics in Acetylcholinesterase
• Name in Czech: Tryptofan jako otocna zaklopka: Dynamika omega smycky v acetylcholinesterase
• Authors: WIESNER, Jiří (203 Czech Republic, guarantor, belonging to the institution), Zdeněk KŘÍŽ (203 Czech Republic, belonging to the institution) and Jaroslav KOČA (203 Czech Republic, belonging to the institution).
• Edition: Modeling Interactions in Biomolecules III, 2007.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Field of Study: 10403 Physical chemistry
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• RIV identification code: RIV/00216224:14310/07:00020680
• Organization unit: Faculty of Science
• Keywords in English: computational chemistry;computer modeling;molecular dynamics;MD;acetycholinesterase;AChE;nerve agent;irreversible inhibition;sarin
• Tags: acetycholinesterase, AChE, computational chemistry, computer modeling, irreversible inhibition, MD, molecular dynamics, nerve agent, sarin

Abstract

Back door to the active site of acetylcholinesterase (AChE) and its involvement in the catalytic cycle of this enzyme are a really controversial subject. The back door could explain the contrast of a very high AChE catalytic efficiency and the narrow and long access to the active site located in the middle of the protein. Back door could facilitate the diffusion of reaction products - choline or acetic acid after the cleavage of acetylcholine. Back door was seen only in a molecular dynamics of AChE, but for a very short times and its existence was not confirmed experimentally. Herein we present a molecular dynamics of AChE, where the back door opening appears on a nanosecond time scale. We also present a molecular dynamics of AChE, where the back door do not open at all, or where large conformational changes of AChE omega loop occur instead of back door opening events. The differences in the AChE dynamical behaviour are caused by different protonation states of two glutamate residues located on bottom of the active site gorge. The two glutamates (Glu202 and Glu450) with addition of Glu334, located in their proximity as a part of catalytic triad, can strengthen the negative electric field on the bottom of the gorge, when unprotonated, or weaken the field, when protonated, or their charge is compensated by a sodium ion. Other alternative ways to AChE active site (side door) and the overall porosity of omega loop are also discussed.

Abstract (in Czech)

Tryptofan jako otocna zaklopka: Dynamika omega smycky v acetylcholinesterase

Links

• GD204/03/H016, research and development project: Name: Strukturní biofyzika makromolekul

Investor: Czech Science Foundation, Structural biophysics of macromolecules

• MSM0021622413, plan (intention): Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment