title: The open gate of the K(V)1.2 channel: quantum calculations show the key role of hydration.
abstract: The open gate of the Kv1.2 voltage-gated potassium channel can just hold a hydrated K(+) ion. Quantum calculations starting from the x-ray coordinates of the channel confirm this, showing little change from the x-ray coordinates for the protein. Water molecules not in the x-ray coordinates, and the ion itself, are placed by the calculation. The water molecules, including their orientation and hydrogen bonding, with and without an ion, are critical for the path of the ion, from the solution to the gate. A sequence of steps is postulated in which the potential experienced by the ion in the pore is influenced by the position of the ion. The gate structure, with and without the ion, has been optimized. The charges on the atoms and bond lengths have been calculated using natural bond orbital calculations, giving K(+) ~0.77 charges, rather than 1.0. The PVPV hinge sequence has been mutated in silico to PVVV (P407V in the 2A79 numbering). The water structure around the ion becomes discontinuous, separated into two sections, above and below the ion. PVPV conservation closely relates to maintaining the water structure. Finally, these results have implications concerning gating.
authors: Department of Chemistry, City College of CUNY, New York, New York.
authors: Alisher M
authors: AM
authors: Kariev
authors: Department of Chemistry, City College of CUNY, New York, New York.
authors: Philipa
authors: P
authors: Njau
authors: Department of Chemistry, City College of CUNY, New York, New York. Electronic address: green@sci.ccny.cuny.edu.
authors: Michael E
authors: ME
authors: Green
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D051663:Kv1.2 Potassium Channel / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011188:Potassium / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D051663:Kv1.2 Potassium Channel; D014867:Water; D011188:Potassium