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This sandbox is in use until August 1, 2011 for UMass Chemistry 423. Others please do not edit this page. Thanks! Chem423 Team Projects: Understanding Drug Mechanisms

Group Members: Chris Brueckner, Daniel Roy, John Clarkson, Justin Srodulski

Template:STRUCTURE 3jpw

Contents

N-methyl-D-aspartate (NMDA) receptor in binding complex with Ketamine

-Try to included methods of receptor functioning.... Mention AMPA receptors, Kainate receptors, NMDA receptors, with respect to glutamate regulation, also similarities of PCP and Ketamine. Make sure to mention the Mg2+ plug in the ionotropic pore of NMDA receptors... how disruption of the ionic flow/balance affects other receptors, and the synapse as a whole.

(I can help you with this if you need me to)


Anything that seems too involved, or not closely related enough we can start throwing into the additional information section. I haven't spoken with Justin, so I have no idea how that's going.


-Chris

Overall Structure

-I think we need at least 3 green scenes... I'll try to have one for PCP and ketamine binding sites, I'm not sure what you need for overall structure. It might be more coherent if we reference specific topics from the introduction.

-Chris

Template:STRUCTURE 1pbq Template:STRUCTURE 2a5t


(note: 1pbq is a good representation of NMDA in open configuration, while 2a5t shows NMDA in closed form).

Drug Binding Site

Image:(S)Ketamine.png
S-Ketamine Structure
Image:PCPMetabolism.png
PCP in reaction with heat.

(Ligand Binding Domains vs Amino Terminal Domains)

(Ketamine) -- Racemic properties, 4x stronger binding affinity for S-Ketamine (see image)

(PCP) -- include discussion of metabolites, heat activated.... Blood-brain-barrier?

(Mg2+)

(Glutamate)

(Glycine)

(D-Serine?)


Additional Features

Credits

John Clarkson: Introduction

Daniel Roy: Overall Structure

Chris Brueckner: Drug Binding Site

Justin Srodulksi: Additional Features


References

  1. test (PCP Metablite image)
  2. (Jerrold Meyer, Psychopharmacology textbook)
  3. (Biochem text book)
  4. (Ketamine-Induced NMDA Receptor Hypofunction as a Model of Memory Impairment and Psychosis)
  5. (The Neuropsychopharmacology of Phencyclidine: From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia)
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