Functional role of the spatial proximity of Asp114(2.50) in TMH 2 and Asn332(7.49) in TMH 7 of the mu opioid receptor.

Abstract:

:We examined whether a proposed spatial proximity between Asp114(2.50) and Asn332(7.49) affected the functional properties of the mu opioid receptor. The D114(2.50)N mutant had reduced binding affinities for morphine, DAMGO and CTAP, but not for naloxone and [3H]diprenorphine; this mutation also abolished agonist-induced increase in [35S]GTPgammaS binding. The N332(7.49)D mutation eliminated detectable binding of either [3H]diprenorphine or [3H]DAMGO. The combined D114(2.50)N-N332(7.49)D mutation restored high affinity binding for [3H]diprenorphine, CTAP and naloxone, and restored partially the binding affinities, potencies and efficacies of morphine and DAMGO. Thus, reciprocal mutations of Asp114(2.50) and Asn332(7.49) compensate for the detrimental effects of the single mutations, indicating that the residues are adjacent in space and that their chemical functionalities are important for ligand binding and receptor activation.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Xu W,Ozdener F,Li JG,Chen C,de Riel JK,Weinstein H,Liu-Chen LY

doi

10.1016/s0014-5793(99)00316-6

keywords:

subject

Has Abstract

pub_date

1999-03-26 00:00:00

pages

318-24

issue

2-3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(99)00316-6

journal_volume

447

pub_type

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