Blog Archives

Hot topics: Agonist-bound crystal structures of the CB1 cannabinoid receptor

Antagonist bound crystal structures of GPCRs are useful in giving an insight into the molecular conformation of a receptor’s inactive state whilst enabling the design of new drugs. However, they prove insufficient to understand the activation mechanism of the receptor

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Hot topics: Identifiers for the 21st century

While identifiers are not a traditional “hot topic” in pharmacology the subject is becoming increasingly important. One of the reasons is that for mechanistic pharmacology the community needs to define (and communicate) identifiers for the key entities of model organism

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Hot topics: X-ray crystal of the apelin receptor

Activation of the apelin receptor by the peptides apelin or Elabela/Toddler mediates vasodilatation and positive inotropic effects in the adult cardiovascular system and knocking out the receptors results in failure of the heart to develop in developing embryos. To date,

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Hot topic: Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474

The historical context for this commentary can be found in this blogpost. This latest report, based on activity-based profiling (ABPP), constitutes the first open biochemical investigation of BIA 10-2474 (1). The ABPP results show it inhibits several lipases that are

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Hot topic: GPR3 and GPR6, novel molecular targets for cannabidiol

Cannabidiol is a major metabolite from the Cannabis plant, although levels vary dependent on genetic, regional, cultivation and other factors.  It lacks the psychotropic nature of THC, but has been reported to have many biological effects, to the extent that

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Hot topic: Selectivity determinants of GPCR–G-protein binding

As a detailed comparative sequence/structure/evolution analysis it is relatively unusual (in a good sense) to see such a bioinformatics article in Nature. This tour de force was a collaboration between MRC Laboratory of Molecular Biology, Cambridge UK and the Department

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Hot topics: Crystal structure of full-length glucagon receptor provides insight into relative orientation of extracellular and transmembrane domains in an inactive conformation and importance of dynamic changes in this orientation for activation

It has been quite challenging to gain high resolution structural insights into an intact class B G protein-coupled receptor, despite previous solution of multiple structures for the two dominant domains, the extracellular domain (ECD) and the transmembrane helical bundle domain

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