title: Water and glycerol permeation through the glycerol channel GlpF and the aquaporin family.
abstract: The 2.2 A resolution crystal structure of GlpF, an E. coli aquaporin that facilitates the flow of glycerol, water and other small solutes, provides much insight into the molecular function and selectivity of aquaporins. Using GlpF and its atomic structure as a paradigm for the ten highly conserved human aquaporins, site-directed mutagenesis has been used to mutate residues that are possibly integral to the structure and function of different aquaporins. X-ray crystallography and other biophysical and molecular simulation methods allows for assessment of these changes at the structural and functional level. Initial attempts to convert the glycerol specific properties of GlpF towards a water specific aquaporin resulted in the shifting of GlpF channel properties towards that of the water aquaporins. This result reveals the great possibility of emulating and deciphering the function of other aquaporins with GlpF via mutagenesis and investigation of structure and function.
authors.affiliation: Department of Biochemistry and Biophysics, School of Medicine, University of California, San Francisco, CA 94143-2240, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Lee
authors.forename: Shahram
authors.initials: S
authors.lastname: Khademi
authors.forename: William
authors.initials: W
authors.lastname: Harries
authors.forename: David
authors.initials: D
authors.lastname: Savage
authors.forename: Larry
authors.initials: L
authors.lastname: Miercke
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stroud
mesh_terms: D020346:Aquaporins / Q000737:chemistry* / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D003198:Computer Simulation; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000502:physiology*; D005990:Glycerol / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D013329:Structure-Activity Relationship; D014867:Water / Q000378:metabolism*
chemical_list: D020346:Aquaporins; D029968:Escherichia coli Proteins; D014867:Water; C078043:GlpF protein, E coli; D005990:Glycerol