Differences in the Central Nervous System Distribution and Pharmacology of the Mouse 5-Hydroxytryptamine-6 Receptor Compared with Rat and Human Receptors Investigated by Radioligand Binding, Site-Directed Mutagenesis, and Molecular Modeling

2003 ◽  
Vol 64 (6) ◽  
pp. 1295-1308 ◽  
Author(s):  
Warren D. Hirst ◽  
Bjarke Abrahamsen ◽  
Frank E. Blaney ◽  
Andrew R. Calver ◽  
Lucia Aloj ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Modeling ◽  
Binding Site ◽  
Radioligand Binding ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
The Central Nervous System

Combination of Molecular Modeling, Site-Directed Mutagenesis, and SAR Studies To Delineate the Binding Site of Pyridopyrimidine Antagonists on the Human CCK1 Receptor

2005 ◽  
Vol 48 (15) ◽  
pp. 4842-4850 ◽  
Author(s):  
Mercedes Martín-Martínez ◽  
Anne Marty ◽  
Maud Jourdan ◽  
Chantal Escrieut ◽  
Elodie Archer ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Binding Site ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Sar Studies ◽  
Cck1 Receptor

ATP-Binding Site of Human Brain Hexokinase As Studied by Molecular Modeling and Site-Directed Mutagenesis†

Biochemistry ◽  
1996 ◽  
Vol 35 (40) ◽  
pp. 13157-13164 ◽  
Author(s):  
Chenbo Zeng ◽  
Alexander E. Aleshin ◽  
Jason B. Hardie ◽  
Robert W. Harrison ◽  
Herbert J. Fromm
Keyword(s):  
Molecular Modeling ◽  
Human Brain ◽  
Binding Site ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Atp Binding ◽  
Atp Binding Site

The Central Benzodiazepine Receptor

2020 ◽  
pp. 68-80
Author(s):  
Michael H. Ossipov
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Binding Site ◽  
Gaba Receptor ◽  
Benzodiazepine Receptor ◽  
Receptor Activation ◽  
Subunit Structure ◽  
Allosteric Site ◽  
Inhibitory Neurotransmitter ◽  
The Central Nervous System

Benzodiazepines have been used clinically now for more than a half century for the management of anxiety and other conditions. Despite their widespread use, only now are their mechanisms of action and their pharmacologic implications, especially with long-term use, beginning to be appreciated. In the central nervous system, benzodiazepines act on an allosteric site of the GABAA receptor to enhance the activity of this inhibitory neurotransmitter. The GABA receptor consists of 5 subunits, which can vary among 19 different subtypes, resulting in a large number of possible configurations for the GABA receptor. Subunit structure can affect the binding of benzodiazepines to the receptor and can alter the nature of the interaction between the benzodiazepine binding site and the GABA binding site, resulting in different levels of receptor activation and allosteric enhancement. Moreover, the distribution of these different subtypes within the central nervous system, with their varying levels of benzodiazepine efficacy, can mean that benzodiazepines can have differential effects among the different sites of the brain. Consequently, in may be possible to design novel drugs that favor particular subunit configurations and thus produce different pharmacologic profiles. Drugs acting at the benzodiazepine site can be agonists, enhancing the activity of GABA; antagonists, blocking the effect of benzodiazepines at the binding site; or inverse agonists, producing an effect antipodal to that of benzodiazepine agonists.

Structural Features of the Glutamate Binding Site in Recombinant NR1/NR2A N-Methyl-d-aspartate Receptors Determined by Site-Directed Mutagenesis and Molecular Modeling

2005 ◽  
Vol 67 (5) ◽  
pp. 1470-1484 ◽  
Author(s):  
Philip E. Chen ◽  
Matthew T. Geballe ◽  
Phillip J. Stansfeld ◽  
Alexander R. Johnston ◽  
Hongjie Yuan ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Binding Site ◽  
Structural Features ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Glutamate Binding
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