Structural model of nicotinic acetylcholine receptor isotypes bound to acetylcholine and nicotine

BACKGROUND: Nicotine is a psychoactive drug presenting a diverse array of biological activities, some positive, such as enhancement of cognitive performances, others negative, such as addiction liability. Ligands that discriminate between the different isotypes of nicotinic acetylcholine receptors (nAChRs) could present improved pharmacology and toxicity profile. RESULTS: Based on the recent crystal structure of a soluble acetylcholine binding protein from snails, we have built atomic models of acetylcholine and nicotine bound to the pocket of four different human nAChR subtypes. The structures of the docked ligands correlate with available biochemical data, and reveal that the determinants for isotype selectivity are relying essentially on four residues, providing diversity of the ligand binding pocket both in terms of Van der Waals boundary, and electrostatic potential. We used our models to screen in silico a large compound database and identify a new ligand candidate that could display subtype selectivity. CONCLUSION: The nAChR-agonist models should be useful for the design of nAChR agonists with diverse specificity profiles

Analysis of genetic diversity among Ixora cultivars (Rubiaceae) using random amplified polymorphic DNA

10.1006/anbo.1997.0454Annals of Botany803355-361ANBO

Seed surface architecture and random amplified polymorphic DNA profiles of Paulownia fortunei, P. tomentosa and their hybrid

10.1006/anbo.1998.0780Annals of Botany832103-107ANBO

Phylogenetic analysis of dipterocarps using random amplified polymorphic DNA markers

10.1006/anbo.1998.0652Annals of Botany82161-65ANBO

Random amplified polymorphic DNA variation among and within selected Ixora (Rubiaceae) populations and mutants

10.1006/anbo.1999.0918Annals of Botany842253-257ANBO

Profiling of hepatocellular proteins by 1D PAGE-MALDI/MS/MS in a rat heat stress model

Frontiers in Bioscience11SUPPL. 32924-292

Crystallization and preliminary X-ray analysis of candoxin, a novel reversible neurotoxin from the Malayan krait Bungarus candidus

10.1107/S0907444903001094Acta Crystallographica - Section D Biological Crystallography593584-586ABCR

Crystallization and preliminary X-ray analysis of bucain, a novel toxin from the Malayan krait Bungarus candidus

Bucain is a three-finger toxin, structurally homologous to snake-venom muscarinic toxins, from the venom of the Malayan krait Bungarus candidus. These proteins have molecular masses of approximately 6000-8000 da and encompass the potent curaremimetic neurotoxins which confer lethality to Elapidae and Hydrophidae venoms. Bucain was crystallized in two crystal forms by the hanging-drop vapour-diffusion technique in 0.1 M sodium citrate pH 5.6, 15% PEG 4000 and 0.15 M ammonium acetate. Form I crystals belong to the monoclinic system space group C2, with unit-cell parameters a = 93.73, b = 49.02, c = 74.09 Angstrom, beta = 111.32degrees, and diffract to a nominal resolution of 1.61 Angstrom. Form II crystals also belong to the space group C2, with unit-cell parameters a = 165.04, b = 49.44, c = 127.60 Angstrom, beta = 125.55degrees, and diffract to a nominal resolution of 2.78 Angstrom. The self-rotation function indicates the presence of four and eight molecules in the crystallographic asymmetric unit of the form I and form II crystals, respectively. Attempts to solve these structures by molecular-replacement methods have not been successful and a heavy-atom derivative search has been initiated