These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Enzymatic activity versus structural dynamics: the case of acetylcholinesterase tetramer.
    Author: Gorfe AA, Lu B, Yu Z, McCammon JA.
    Journal: Biophys J; 2009 Aug 05; 97(3):897-905. PubMed ID: 19651048.
    Abstract:
    The function of many proteins, such as enzymes, is modulated by structural fluctuations. This is especially the case in gated diffusion-controlled reactions (where the rates of the initial diffusional encounter and of structural fluctuations determine the overall rate of the reaction) and in oligomeric proteins (where function often requires a coordinated movement of individual subunits). A classic example of a diffusion-controlled biological reaction catalyzed by an oligomeric enzyme is the hydrolysis of synaptic acetylcholine (ACh) by tetrameric acetylcholinesterase (AChEt). Despite decades of efforts, the extent to which enzymatic efficiency of AChEt (or any other enzyme) is modulated by flexibility is not fully determined. This article attempts to determine the correlation between the dynamics of AChEt and the rate of reaction between AChEt and ACh. We employed equilibrium and nonequilibrium electro-diffusion models to compute rate coefficients for an ensemble of structures generated by molecular dynamics simulation. We found that, for the static initial model, the average reaction rate per active site is approximately 22-30% slower in the tetramer than in the monomer. However, this effect of tetramerization is modulated by the intersubunit motions in the tetramer such that a complex interplay of steric and electrostatic effects either guides or blocks the substrate into or from each of the four active sites. As a result, the rate per active site calculated for some of the tetramer structures is only approximately 15% smaller than the rate in the monomer. We conclude that structural dynamics minimizes the adverse effect of tetramerization, allowing the enzyme to maintain similar enzymatic efficiency in different oligomerization states.
    [Abstract] [Full Text] [Related] [New Search]