Acetylcholinesterase: enhanced fluctuations and alternative routes to the active site in the complex with fasciculin-2

J Am Chem Soc. 2004 Jun 16;126(23):7198-205. doi: 10.1021/ja0485715.

Abstract

A 15 ns molecular dynamics simulation is reported for the complex of mouse acetylcholinesterase (mAChE) and the protein neurotoxin fasciculin-2. As compared to a 15 ns simulation of apo-mAChE, the structural fluctuations of the enzyme are substantially increased in magnitude for the enzyme in the complex. Fluctuations of part of the long omega loop (residues 69-96) are particularly enhanced. This loop forms one wall of the active site, and the enhanced fluctuations lead to additional routes of access to the active site.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Acetylcholinesterase / metabolism*
  • Acylation
  • Binding Sites
  • Elapid Venoms / chemistry*
  • Elapid Venoms / metabolism*
  • Fluorescence Polarization
  • Models, Molecular
  • Pliability
  • Protein Binding
  • Protein Conformation

Substances

  • Elapid Venoms
  • fasciculin
  • Acetylcholinesterase