Turned on the computer, pulled up the feed reader and found a post by Keith Robison about only the 2nd GPCR crystal structure, at least one publicly available. He mentions the first structure (published in 2000). I have several issues with that structure, since pretty much half my PhD was done with models based on early cryoelectron microscopy and theoretical traces of the rhodopsin structure. Of course with the structure appearing just months before I finished up, there was a frantic attempt to redo many of the calculations I had done, just to make sure that the structure didn’t end up making all that work completely wrong. Luckily, things ended up just fine.
Anyway, not surprisingly, structure #2 belongs to the beta-2-adrenergic receptor, B2AR (it has been rumored to have been solved previously as well). I know many people who’ve been trying to solve membrane protein structures. For them, this will be both an exciting day and one of frustration, since they would have loved to have been the ones. I have been out of the field for a while, so I only saw a couple of familiar names in the list of authors from the Science and Nature papers, Gerhard Schertler, who’s been in this field for a very very long time and Ray Stevens.
Not surprisingly, the B2AR structure is different from rhodopsin, lending credence to the theory that many of us have had about the limited availability of homology modeling methods that used rhopdopsin as a template. However, I believe that the general rules developed by Baldwin, et al, many years ago (an early example of bioinformatics) are still in place. Unfortunately, the structure is not yet available on the PDB (at least I couldn’t find it. If I find a structure, I will update this post.
Will this structure open the floodgates? The pharma industry certainly hopes so.
It took a while!!!
Turned on the computer, pulled up the feed reader and found a post by Keith Robison about only the 2nd GPCR crystal structure, at least one publicly available. He mentions the first structure (published in 2000). I have several issues with that structure, since pretty much half my PhD was done with models based on early cryoelectron microscopy and theoretical traces of the rhodopsin structure. Of course with the structure appearing just months before I finished up, there was a frantic attempt to redo many of the calculations I had done, just to make sure that the structure didn’t end up making all that work completely wrong. Luckily, things ended up just fine.
Anyway, not surprisingly, structure #2 belongs to the beta-2-adrenergic receptor, B2AR (it has been rumored to have been solved previously as well). I know many people who’ve been trying to solve membrane protein structures. For them, this will be both an exciting day and one of frustration, since they would have loved to have been the ones. I have been out of the field for a while, so I only saw a couple of familiar names in the list of authors from the Science and Nature papers, Gerhard Schertler, who’s been in this field for a very very long time and Ray Stevens.
Not surprisingly, the B2AR structure is different from rhodopsin, lending credence to the theory that many of us have had about the limited availability of homology modeling methods that used rhopdopsin as a template. However, I believe that the general rules developed by Baldwin, et al, many years ago (an early example of bioinformatics) are still in place. Unfortunately, the structure is not yet available on the PDB (at least I couldn’t find it. If I find a structure, I will update this post.
Will this structure open the floodgates? The pharma industry certainly hopes so.
Technorati Tags: GPCR, Structural Biology