Alternative entrances into the acetylcholinesterase active site

WIESNER, Jiří, Zdeněk KŘÍŽ and Jaroslav KOČA. Alternative entrances into the acetylcholinesterase active site. In Strukturní biofyzika makromolekul II. 2007.

Basic information

Original name

Alternative entrances into the acetylcholinesterase active site

Name in Czech

Alternativní vstupy do aktivního místa acetylcholinesterasy

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

Strukturní biofyzika makromolekul II, 2007

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Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

10403 Physical chemistry

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14310/07:00020234

Organization unit

Faculty of Science

Keywords in English

computational chemistry;computer modeling;molecular dynamics;MD;acetycholinesterase;AChE;alternative entrances;back door;side door;Trp86;Trp84

Tags

acetycholinesterase, AChE, alternative entrances, back door, computational chemistry, computer modeling, MD, molecular dynamics, side door, Trp84, Trp86

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Abstract

V originále

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.

In Czech

Alternativní vstupy do aktivního místa acetylcholinesterasy

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Links

GD204/03/H016, research and development project	Name: Strukturní biofyzika makromolekul Investor: Czech Science Foundation, Structural biophysics of macromolecules
LC06030, research and development project	Name: Biomolekulární centrum Investor: Ministry of Education, Youth and Sports of the CR, Biomolecular centre
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