A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore.

A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. Research Abstract Details 

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A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. Abstract Text:

Zhe Yang,Brett A Cromer,Robert J Harvey,Michael W Parker,Joseph W Lynch,

Picrotoxin, an antagonist of structurally-rated GABA(A) receptors (GABA(A)Rs) and glycine receptors (GlyRs), is an equimolar mixture of picrotoxinin (PTXININ) and picrotin (PTN). These compounds share a common structure except that PTN contains a slightly larger dimethylmethanol in place of the PTXININ isopropenyl group. Although the homomeric alpha1 GlyR is equally sensitive to both compounds, we show here that homomeric alpha2 and alpha3 GlyRs, like most GABA(A)Rs, are selectively inhibited by PTXININ. As conservative mutations to pore-lining 6' threonines equally affect the sensitivity of the alpha1 GlyR to both compounds, we conclude that PTXININ and PTN bind to 6' threonines by hydrogen bonding with exocyclic oxygens common to both molecules. In contrast, substitution of the 2' pore-lining glycine by serine selectively reduces PTN sensitivity, whereas the introduction of 2' alanines selectively increases PTXININ sensitivity. These results define the orientation of PTXININ and PTN binding in the alpha1 GlyR pore and allow us to conclude that the relatively reduced sensitivity of PTN at GABA(A)Rs and alpha2 and alpha3 GlyRs is due predominantly to its larger size and reduced ability to form hydrophobic interactions with 2' alanines.

A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. Publishing Authors By Initials

Z Yang,BA Cromer,RJ Harvey,MW Parker,JW Lynch,

For similar nervous system: synapses research abstracts see: nervous system: synapses research

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A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of neurochemistry

VOLUME: 103

Page Numbers: 580-9

Journal Abbreviation: J. Neurochem.

ISSN: 0022-3042

DAY: 20

MONTH: 08

YEAR: 2007

A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. Information

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LANGUAGE: eng

NlmUniqueID: 2985190

A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. Keywords Mesh Terms:

KEYWORDS: Synapses

MESH TERMS: drug effects

Chemical & Substance for Abstract: A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore. Information

Substance Name: Glycine

Registry Number: 56-40-6

Grant and Affiliation Information for A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor pore.

AFFILIATION: School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.

Country: England

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MEDLINETA: J Neurochem

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