Poster Presentation 2014 International Biophysics Congress

Detecting a dynamic nature of the molecular tunnel in tryptophan synthase (#683)

Midori Yano 1 , Kei Yura 2 3
  1. Department of Computer Science, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan
  2. Department of Biological Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan
  3. National Institute of Genetics, Shizuoka, Japan

Tryptophan synthase is an (ab)2 hetero tetramer enzyme with a molecular tunnel between the a and b subunits. The tunnel connects the active sites of each subunit and is apparently a path for indole, the product of the a subunit, to the active site of the b subunit where a trypotophan is synthesized. The tunnel is considered to facilitate the high productivity of the enzyme by reducing the chance of indole to be diffused into the bulk water. Since the discovery of the molecular tunnel in 1988, the tunnel has been considered to play a passive role in enzymatic reaction, namely a static path for the molecule. In Protein Data Bank (PDB), more than 50 different coordinate data obtained in different conditions or different species of tryptophan synthase have been registered, and this wealth of information let us address the question whether the tunnel is dynamic or static by comparing the detail of the tunnel structures. To address this question, we developed an automatic and fast method to detect a molecular tunnel in protein complex out of its three-dimensional structure data. Application of this new method to the whole coordinates of tryptophan synthase in PDB showed that the form of the tunnel heavily depends on the condition of the enzyme. In some cases, the path of the potential tunnel is blocked by a group of atoms apparently closing the tunnel and enabling active manipulation of the substrate. This finding suggests that the form of the tunnel is not static, but quite dynamic and the enzyme actively regulate the transport of the substrate.