2om9: Difference between revisions
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New page: left|200px<br /> <applet load="2om9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2om9, resolution 2.80Å" /> '''Ajulemic acid, a sy... |
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[[Image:2om9.gif|left|200px]]<br /> | [[Image:2om9.gif|left|200px]]<br /><applet load="2om9" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2om9" size=" | |||
caption="2om9, resolution 2.80Å" /> | caption="2om9, resolution 2.80Å" /> | ||
'''Ajulemic acid, a synthetic cannabinoid bound to PPAR gamma'''<br /> | '''Ajulemic acid, a synthetic cannabinoid bound to PPAR gamma'''<br /> | ||
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==Overview== | ==Overview== | ||
Ajulemic acid (AJA) is a synthetic analog of THC-11-oic acid, a metabolite, of tetrahydrocannabinol (THC), the major active ingredient of the, recreational drug marijuana derived from the plant Cannabis sativa. AJA, has potent analgesic and anti-inflammatory activity in vivo, but without, the psychotropic action of THC. However, its precise mechanism of action, remains unknown. Biochemical studies indicate that AJA binds directly and, selectively to the isotype gamma of the peroxisome proliferator-activated, receptor (PPARgamma) suggesting that this may be a pharmacologically, relevant receptor for this compound and a potential target for drug, development in the treatment of pain and inflammation. Here, we report the, crystal structure of the ligand binding domain of the gamma isotype of, human PPAR in complex with ajulemic acid, determined at 2.8-A resolution., Our results show a binding mode that is compatible with other known, partial agonists of PPAR, explaining their moderate activation of the, receptor, as well as the structural basis for isotype selectivity, as, observed previously in vitro. The structure also provides clues to the, understanding of partial agonism itself, suggesting a rational approach to, the design of molecules capable of activating the receptor at levels that, avoid undesirable side effects. | Ajulemic acid (AJA) is a synthetic analog of THC-11-oic acid, a metabolite, of tetrahydrocannabinol (THC), the major active ingredient of the, recreational drug marijuana derived from the plant Cannabis sativa. AJA, has potent analgesic and anti-inflammatory activity in vivo, but without, the psychotropic action of THC. However, its precise mechanism of action, remains unknown. Biochemical studies indicate that AJA binds directly and, selectively to the isotype gamma of the peroxisome proliferator-activated, receptor (PPARgamma) suggesting that this may be a pharmacologically, relevant receptor for this compound and a potential target for drug, development in the treatment of pain and inflammation. Here, we report the, crystal structure of the ligand binding domain of the gamma isotype of, human PPAR in complex with ajulemic acid, determined at 2.8-A resolution., Our results show a binding mode that is compatible with other known, partial agonists of PPAR, explaining their moderate activation of the, receptor, as well as the structural basis for isotype selectivity, as, observed previously in vitro. The structure also provides clues to the, understanding of partial agonism itself, suggesting a rational approach to, the design of molecules capable of activating the receptor at levels that, avoid undesirable side effects. | ||
==About this Structure== | ==About this Structure== | ||
2OM9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with AJA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2OM9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=AJA:'>AJA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OM9 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: ppar gamma]] | [[Category: ppar gamma]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:22:58 2008'' | ||
