TY - JOUR
T1 - What makes an aquaporin a glycerol channel? A comparative study of AqpZ and GlpF
AU - Wang, Yi
AU - Schulten, Klaus
AU - Tajkhorshid, Emad
N1 - Funding Information:
This work is supported by National Institutes of Health grants P41-RR05969 and R01-GM067887. The authors gladly acknowledge supercomputer time provided by the Pittsburgh Supercomputer Center and the National Center for Supercomputing Applications via National Resources Allocation Committee grant MCA93S028.
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.str.2005.05.005
DO - 10.1016/j.str.2005.05.005
M3 - Article
C2 - 16084383
AN - SCOPUS:23044496908
SN - 0969-2126
VL - 13
SP - 1107
EP - 1118
JO - Structure
JF - Structure
IS - 8
ER -