Structural Studies on D-2 Dopamine-Receptors - Mutation of a Histidine Residue Specifically Affects the Binding of a Subgroup of Substituted Benzamide Drugd

Woodward, R. and Daniell, S.J and Strange, Philip G. and Naylor, Louise H. (1994) Structural Studies on D-2 Dopamine-Receptors - Mutation of a Histidine Residue Specifically Affects the Binding of a Subgroup of Substituted Benzamide Drugd. Journal of Neurochemistry, 62 (5). pp. 1664-1669. ISSN 0022-3042. (The full text of this publication is not available from this repository)

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Abstract

A histidine residue (His(394)) that is likely to be located in the ligand-binding region of the D-2 dopamine receptor has been mutated to a leucine (Leu(394)), and the properties of the mutant receptor have been determined. For a range of antagonists the mutation has only a minor effect on the affinity of the receptor for the antagonist. The mutation does, however, elicit a structurally specific effect on the affinity with which certain members of the substituted benzamide class of antagonist bind to the receptor. Some of these drugs, e.g., sulpiride, sultopride, and tiapride, bind with reduced affinity to the mutated receptor, whereas others, e.g., clebopride and metoclopramide, bind with increased affinity. However, the Na+/H+ sensitivity of the binding of sulpiride to the receptor is not reduced by the mutation. These findings have been interpreted in terms of the productive or unfavourable interaction of the His(394) residue with these compounds.

Item Type: Article
Uncontrolled keywords: D-2 DOPAMINE RECEPTOR; MUTAGENESIS; LIGAND BINDING; HISTIDINE RESIDUE; SUBSTITUTED BENZAMIDES
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: P. Ogbuji
Date Deposited: 09 Jun 2009 13:42
Last Modified: 17 Apr 2014 08:44
Resource URI: http://kar.kent.ac.uk/id/eprint/20112 (The current URI for this page, for reference purposes)
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