differential role of the menthol-binding residue y745 in the antagonism of thermally gated trpm8 channels
Article Quality & Performance Metrics
Readership in this journal
PopularRanked #9 of 99 articles by views in fems microbiology ecology
Bar heights use a square-root scale.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
Abstract
Abstract
Background
TRPM8 is a non-selective cation channel that belongs to the melastatin subfamily of the transient receptor potential (TRP) ion channels. TRPM8 is activated by voltage, cold and cooling compounds such as menthol. Despite its essential role for cold temperature sensing in mammals, the pharmacology of TRPM8 is still in its infancy. Recently, tyrosine 745 (Y745) was identified as a critical residue for menthol sensitivity of the channel. In this report, we study the effect of mutating this residue on the action of several known TRPM8 antagonists: BCTC, capsazepine, SKF96365, and clotrimazole as well as two new inhibitor candidates, econazole and imidazole.
Results
We show that Y745 at the menthol binding site is critical for inhibition mediated by SKF96365 of cold- and voltage-activated TRPM8 currents. In contrast, the inhibition by other antagonists was unaffected by the mutation (BCTC) or only partially reduced (capsazepine, clotrimazole, econazole), suggesting that additional binding sites exist on the TRPM8 channel from where the inhibitors exert their negative modulation. Indeed, a molecular docking model implies that menthol and SKF96365 interact readily with Y745, while BCTC is unable to bind to this residue.
Conclusion
In summary, we identify structural elements on the TRPM8 channel that are critical for the action of channel antagonists, providing valuable information for the future design of new, specific modulator compounds.
| Reference Key |
antonio2009moleculardifferential
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | ;Ferrer-Montiel Antonio;Fernández-Ballester Gregorio;Pertusa María;Malkia Annika;Viana Félix |
| Journal | fems microbiology ecology |
| Year | 2009 |
| DOI |
10.1186/1744-8069-5-62
|
| URL | |
| Keywords |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
ZincirX productsfrom the team behind Journament
-
PatentYazar
Patent drafts for the EPO, USPTO and TürkPatent
From inventor notes to a DOCX draft: description, claims, abstract. The machine drafts, the attorney signs.
See how it works (opens in a new tab) -
Projenator
Have a project idea? Score and plan it with AI
AI scores your idea in five dimensions and builds a phased plan. Your first project is free, no card needed.
Start your first project (opens in a new tab)
Cookies
We use strictly necessary cookies to run the site and keep you signed in. With your permission we would also use Google Analytics to see how the site is used, and Google AdSense to show ads on journal and article pages. Both stay off unless you accept, and you can change your mind at any time. How we use cookies · KVKK notice (Türkiye)
Cookie settings
Comments
No comments yet. Be the first to comment on this article.