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== '''Drug Binding Site''' == | == '''Drug Binding Site''' == | ||
[[Image:(S)Ketamine.png|thumb|S-Ketamine Structure]] | [[Image:(S)Ketamine.png|thumb|Figure 3: S-Ketamine Structure]] | ||
[[Image:PCPMetabolism.png|thumb|PCP in reaction with heat.]] | [[Image:PCPMetabolism.png|thumb|Figure 4: PCP in reaction with heat.]] | ||
The NMDA Receptor primarily functions as a specific type of glutamate receptor. In addition to binding NMDA, its namesake, the receptor also contains binding sites for a wide variety of other molecules, most notably Benzodiazepines, D-serine, and Glycine. These binding sites occur extracellularly along the ligand binding domain (LBD). Glutamate binding alone is not enough to trigger a conformational change. In order to open the ion-channel, the NMDA receptor makes use of either Glycine or D-Serine, which are co-agonists. These two molecules comptete for the same binding site, and only their binding in conjunction with Glutamate can alter the protein's shape to expose the ion-channel. Furthermore, this allows the Mg2+ plug to be ejected from the pore during cellular depolarization-- the final stage before ion transport can begin. | The NMDA Receptor primarily functions as a specific type of glutamate receptor. In addition to binding NMDA, its namesake, the receptor also contains binding sites for a wide variety of other molecules, most notably Benzodiazepines, D-serine, and Glycine. These binding sites occur extracellularly along the ligand binding domain (LBD). Glutamate binding alone is not enough to trigger a conformational change. In order to open the ion-channel, the NMDA receptor makes use of either Glycine or D-Serine, which are co-agonists. These two molecules comptete for the same binding site, and only their binding in conjunction with Glutamate can alter the protein's shape to expose the ion-channel. Furthermore, this allows the Mg2+ plug to be ejected from the pore during cellular depolarization-- the final stage before ion transport can begin. | ||
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As shown in figures 3 and 4, Ketamine and PCP both share similar cyclic carbon structures which can easily bind and block such a narrow opening. Ketamine itself has racemic properties, and it has been shown that (s)-Ketamine has a four-fold increase in binding affinity for the NMDA receptor. PCP has shown to have an even greater binding affinity, to the point where it causes severe damage to the protein structure through its inhibitory nature. Given that PCP is often smoked in recreational abuse, the heat causes a reaction that breaks the molecule down into 1-phenyl-1-cyclohexene (PC) and piperidine. PC is most likely the molecule that ultimate binds to the ion-channel, given it's close structural similarities to Ketamine. | As shown in figures 3 and 4, Ketamine and PCP both share similar cyclic carbon structures which can easily bind and block such a narrow opening. Ketamine itself has racemic properties, and it has been shown that (s)-Ketamine has a four-fold increase in binding affinity for the NMDA receptor. PCP has shown to have an even greater binding affinity, to the point where it causes severe damage to the protein structure through its inhibitory nature. Given that PCP is often smoked in recreational abuse, the heat causes a reaction that breaks the molecule down into 1-phenyl-1-cyclohexene (PC) and piperidine. PC is most likely the molecule that ultimate binds to the ion-channel, given it's close structural similarities to Ketamine. | ||
[[Image:NMDAR.jpg|Figure 5: NMDA Receptor Simplified]] | |||
{{STRUCTURE_3jpy | PDB=3jpy | SCENE= }} | {{STRUCTURE_3jpy | PDB=3jpy | SCENE= }} | ||
