title: A possible molecular mechanism for the interaction of defensin with the sensory neuron membrane.
abstract: A local membrane potential clamping method was used to study the effects of defensin NP-1 on the membranes of rat spinal ganglion neurons. NP-1 led to decreases in the effective charge for the activation gating system. This process depended on the NP-1 concentration. Use of the Hill equation showed that Kd was 2.10(-12) M and the Hill coefficient was 0.9. The structure of the defensin molecule was optimized using quantum chemical calculations based on a molecular mechanics method. The results obtained from these calculations suggested that a single hydroxyl group directed towards the outer part of thedefensin molecule and forming the carboxyl group of amino acid Glu14 could form a hydrogen bond with the active center of the membrane receptor. This explains the experimentally observed 1:1 stoichiometry of the ligand-receptor binding interaction between the defensin and the sensory neuron membrane.
authors.affiliation: I. P. Pavlov Institute of Physiology, St. Petersburg, Russia.
authors.forename: V B
authors.initials: VB
authors.lastname: Plakhova
authors.forename: B F
authors.initials: BF
authors.lastname: Shchegolev
authors.forename: I V
authors.initials: IV
authors.lastname: Rogachevskii
authors.forename: A D
authors.initials: AD
authors.lastname: Nozdrachev
authors.forename: B V
authors.initials: BV
authors.lastname: Krylov
authors.forename: S A
authors.initials: SA
authors.lastname: Podzorova
authors.forename: V N
authors.initials: VN
authors.lastname: Kokryakov
mesh_terms: D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000502:physiology; D023082:Defensins / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D008958:Models, Molecular; D008968:Molecular Conformation; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011789:Quantum Theory; D011817:Rabbits; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D023082:Defensins; D015222:Sodium Channels; D013779:Tetrodotoxin