Crystal structure of naltrexone hydrochloride: implications for location of the nicotinic receptor noncompetitive inhibitor binding site

A.C. Le Dain, Barry Madsen, B. Skelton, A.H. White

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    Abstract

    The opiate receptor antagonist naltrexone is also a non-competitive blocker of the nicotinic acetylcholine receptor ion channel complex. This blockade is usually thought to be due to physical occlusion of the channel pore. However, the most recent structural data for the nicotinic receptor show that the pore is generally 20-25 angstrom in diameter, with a much narrower section in the plane of the membrane which is presumed to be the gating region. We have completed a single-crystal X-ray structure determination of naltrexone hydrochloride, (C20H24NO4)+ Cl-.4H2O, at room temperature. Crystals are orthorhombic, P2(1)2(1)2(1), a 18.099(5), b 15.926(6), c 7.768(11) angstrom, Z 4; the structure was refined to a residual of 0-056 for 1988 'observed' reflections. The maximal dimension of this molecule (c. 11.6 angstrom) suggests that physical occlusion of the channel pore can only occur if binding is directly in the gating region.
    Original languageEnglish
    Pages (from-to)635-640
    JournalAustralian Journal of Chemistry: an international journal for chemical science
    Volume45
    DOIs
    Publication statusPublished - 1992

    Fingerprint

    Naltrexone
    Nicotinic Receptors
    Crystal structure
    Binding Sites
    Opioid Receptors
    Ion Channels
    Single crystals
    Membranes
    X rays
    Crystals
    Molecules
    Temperature

    Cite this

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    title = "Crystal structure of naltrexone hydrochloride: implications for location of the nicotinic receptor noncompetitive inhibitor binding site",
    abstract = "The opiate receptor antagonist naltrexone is also a non-competitive blocker of the nicotinic acetylcholine receptor ion channel complex. This blockade is usually thought to be due to physical occlusion of the channel pore. However, the most recent structural data for the nicotinic receptor show that the pore is generally 20-25 angstrom in diameter, with a much narrower section in the plane of the membrane which is presumed to be the gating region. We have completed a single-crystal X-ray structure determination of naltrexone hydrochloride, (C20H24NO4)+ Cl-.4H2O, at room temperature. Crystals are orthorhombic, P2(1)2(1)2(1), a 18.099(5), b 15.926(6), c 7.768(11) angstrom, Z 4; the structure was refined to a residual of 0-056 for 1988 'observed' reflections. The maximal dimension of this molecule (c. 11.6 angstrom) suggests that physical occlusion of the channel pore can only occur if binding is directly in the gating region.",
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    TY - JOUR

    T1 - Crystal structure of naltrexone hydrochloride: implications for location of the nicotinic receptor noncompetitive inhibitor binding site

    AU - Le Dain, A.C.

    AU - Madsen, Barry

    AU - Skelton, B.

    AU - White, A.H.

    PY - 1992

    Y1 - 1992

    N2 - The opiate receptor antagonist naltrexone is also a non-competitive blocker of the nicotinic acetylcholine receptor ion channel complex. This blockade is usually thought to be due to physical occlusion of the channel pore. However, the most recent structural data for the nicotinic receptor show that the pore is generally 20-25 angstrom in diameter, with a much narrower section in the plane of the membrane which is presumed to be the gating region. We have completed a single-crystal X-ray structure determination of naltrexone hydrochloride, (C20H24NO4)+ Cl-.4H2O, at room temperature. Crystals are orthorhombic, P2(1)2(1)2(1), a 18.099(5), b 15.926(6), c 7.768(11) angstrom, Z 4; the structure was refined to a residual of 0-056 for 1988 'observed' reflections. The maximal dimension of this molecule (c. 11.6 angstrom) suggests that physical occlusion of the channel pore can only occur if binding is directly in the gating region.

    AB - The opiate receptor antagonist naltrexone is also a non-competitive blocker of the nicotinic acetylcholine receptor ion channel complex. This blockade is usually thought to be due to physical occlusion of the channel pore. However, the most recent structural data for the nicotinic receptor show that the pore is generally 20-25 angstrom in diameter, with a much narrower section in the plane of the membrane which is presumed to be the gating region. We have completed a single-crystal X-ray structure determination of naltrexone hydrochloride, (C20H24NO4)+ Cl-.4H2O, at room temperature. Crystals are orthorhombic, P2(1)2(1)2(1), a 18.099(5), b 15.926(6), c 7.768(11) angstrom, Z 4; the structure was refined to a residual of 0-056 for 1988 'observed' reflections. The maximal dimension of this molecule (c. 11.6 angstrom) suggests that physical occlusion of the channel pore can only occur if binding is directly in the gating region.

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    JF - Australian Journal of Chemistry:an international journal for chemical science

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