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Structure
Ligand Binding Pocket
Near the top of the protein is the
This pocket is comprised of several key amino acid resides. The first reside is a Phenylalanine at position F358. The purpose of this amino acid is to take part in a network of hydrophobic stacking interactions. These interactions stabilize the Y324 and W321 residues. These are crucial interactions because the Y324 is the amino acid residue that directly interacts with the
via https://en.wikipedia.org/wiki/Van_der_Waals_force Van der Waals interactions.
Without the hydrophobic stacking interactions that are facilitated by the F358 this binding interaction would not occur. The W321 residue also partakes in these stacking interactions. The W321 serves as the boundary between the ligand binding pocket and the sodium binding pocket.
Biological Relevance
Leptin Research
A study was done by Liang Y. et al.to analyze the effects that being NTSR1 deficient had on mice. The results demonstrated that mice who were NTSR1 deficient were not able to receive a satiety signal.This resulted in the mice to continuing to eat as long as food was present, leading to significant weight gain. This is due to the fact that NTSR1 is involved in a signaling pathway that regulates leptin and therefore food intake. Without sufficient NTSR1 this pathway is interrupted. https://en.wikipedia.org/wiki/Leptin
Cancer Studies
It has been shown that some tumor cells can secrete and express Neurotensin receptors themselves suggetsing that autocrine, endocrine and paracrine regulation by Neurotensin are possible. This leads to aggressive growth and possibly tumor development. A study was done that demonstrated that injecting animals with Neurotensin increased tumor growth and size, while injecting them with Neurotensin antagonist decreased tumor growth.It is believed that Neurotensin regulation may be used in future cancer treatment techniques.
Schizophrenia Research
The Dopamine Hypothesis http://www.schizophreniaforum.org/for/curr/AbiDargham/ states that having hyperdopamine levels may lead to schizophrenic symptoms. It has been shown that NTSR1 caused a blockade which inhibited firing in dopaminergic cells. It is believed that NTSR1 could therefore be used as a therapeutic for treating schizophrenia.Although this research is promising, the secondary effects were too extreme and the trial was discontinued.This is a pathway where NTSR1 research is focused on that could lead to ground breaking advances in treating schizophrenia.
Structural highlights
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