What makes an aquaporin a glycerol channel? A comparative study of AqpZ and GlpF

Structure. 2005 Aug;13(8):1107-18. doi: 10.1016/j.str.2005.05.005.


The recent availability of high-resolution structures of two structurally highly homologous, but functionally distinct aquaporins from the same species, namely Escherichia coli AqpZ, a pure water channel, and GlpF, a glycerol channel, presents a unique opportunity to understand the mechanism of substrate selectivity in these channels. Comparison of the free energy profile of glycerol conduction through AqpZ and GlpF reveals a much larger barrier in AqpZ (22.8 kcal/mol) than in GlpF (7.3 kcal/mol). In either channel, the highest barrier is located at the selectivity filter. Analysis of substrate-protein interactions suggests that steric restriction of AqpZ is the main contribution to this large barrier. Another important difference is the presence of a deep energy well at the periplasmic vestibule of GlpF, which was not found in AqpZ. The latter difference can be attributed to the more pronounced structural asymmetry of GlpF, which may play a role in attracting glycerol.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aquaporins / genetics
  • Aquaporins / metabolism*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Glycerol / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*


  • Aquaporins
  • Escherichia coli Proteins
  • Membrane Proteins
  • aqpZ protein, E coli
  • GlpF protein, E coli
  • Glycerol