5HT2A Receptor - work still in progress?

Case number:845799-996687
Topic:Biochem
Opened by:BCAA
Status:Open
Type:Question
Opened on:Friday, January 17, 2014 - 21:04
Last modified:Sunday, January 19, 2014 - 08:09

Can someone please tell me, if the precise 3D structure of the 5‐HT2A receptor has already been determined?

I looked at:

http://www.uniprot.org/uniprot/P28223

and it doesn't tell me, if work is still in progress...

Thanks,

BCAA

(Fri, 01/17/2014 - 21:04  |  6 comments)


wisky's picture
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I did not read the entire thread, but this might have something you're looking for. The 5-HT-2A receptor has been modeled at least well enough to model ligand-receptor interactions

http://bluelight.org/vb/threads/591265-modeling-the-5-HT-2a-receptor

wisky's picture
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25I-NBOMe is a personal favorite of mine ;)

BCAA's picture
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Wisky, you make me laugh :))

>> 25I-NBOMe is a personal favorite of mine ;)

You mean the rendering in the thread or the substance itself? ;))

Well, I'm very aware of that substance and also of the the thread, that I discovered yesterday. I was also reading all the papers regarding the development of the Nbomes series, very interesting stuff.

Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain
http://bitnest.ca/external.php?id=%2518%253A3%25172%251BE%2524K%255BG%2521%2524%257D%2504%2504V

And that's why my question comes up. The author states on p. 55:

"The three dimensional structure of the 5‐HT2A receptor has not yet been determined, which is due to the general problems involved in crystallizing GPCRs "

This was in 2010. Now does this still apply? Because a precise 3D structure of the 5‐HT2A receptor would result in better agonists (like Nbomes) and better antagonists (like risperidone). And I can tell you that the latter one really needs some overhauling.

BCAA's picture
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Vignir Isberg, et. al.: "G Protein- and Agonist-Bound Serotonin 5-HT2A Receptor Model Activated by Steered Molecular Dynamics Simulations" dx.doi.org/10.1021/ci100402f | J. Chem. Inf. Model. 2011, 51, 315–325:

"Active GPCR structures are highly needed for activation studies and ligand design, but modeling of active-state GPCRs has been, and still is, very challenging due to the limited number of related experimental structures."

wisky's picture
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From the information I've read, it would appear the 5HT2A receptor structure has not been solved. I unfortunately have no references to give you right now... I used to have access to huge volumes of research journals online through my university, but now that I'm no longer enrolled, I'm stuck looking for free papers.

The 5HT2A receptor is 471 residues in length, and Foldit has a 500 residue length freestyle design contest that you could try out if you wanted to solve for the structure yourself (a 30 residue tail shouldn't affect the whole fold too drastically).

I downloaded that thesis you linked me to and will be reading it soon. As far as 25I-NBOMe goes, I was definitely just referring to the substance itself :).

BCAA's picture
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>> I'm stuck looking for free papers.

Well, try libgen.org/scimag/ - maybe with a proxy if you are located in the US. sci-hub.org was/is blocked for US vistors, I'm not sure if this applies for it's sister site.

The GPCR research is an active field as I discovered yesterday. According to http://gpcr.scripps.edu
there hasn't been much discovered yet.

>> Foldit has a 500 residue length freestyle design contest

Yes, I've seen the 500 residue contest, it works surprisingly smooth for that much residues. This leads me to the question if the Foldit team could host a 5HT2A Receptor contest. Do you know who could set up one and make it happen?

The model from 10.1021/ci100402f is available here: http://pubs.acs.org/doi/suppl/10.1021/ci100402f/suppl_file/ci100402f_si_001.pdf - somebody could convert it into a Foldit model and set up a contest, maybe we could even improve the model! Would you like to play it, too, or is it just me?

>> I downloaded that thesis you linked me to and will be reading it soon.

Yeah the thesis is well-written, definitely worth reading.

>> As far as 25I-NBOMe goes, I was definitely just referring to the substance itself :)

2C-E has a nice structure as well. ^_^

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