Structural highlights
6k41 is a 5 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Gene: | GNAO1 (HUMAN), Gnb1 (LK3 transgenic mice), GNG2 (HUMAN), ADRA2B, ADRA2L1, ADRA2RL1 (HUMAN) |
| Activity: | Lysozyme, with EC number 3.2.1.17 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[GNAO_HUMAN] Early infantile epileptic encephalopathy. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
[GBG2_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity). [GBB1_MOUSE] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity). [GNAO_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(o) protein function is not clear. Stimulated by RGS14. [ADA2A_BOVIN] Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (By similarity).
Publication Abstract from PubMed
The alpha2 adrenergic receptors (alpha2ARs) are G protein-coupled receptors (GPCRs) that respond to adrenaline and noradrenaline and couple to the Gi/o family of G proteins. alpha2ARs play important roles in regulating the sympathetic nervous system. Dexmedetomidine is a highly selective alpha2AR agonist used in post-operative patients as an anxiety-reducing, sedative medicine that decreases the requirement for opioids. As is typical for selective alphaAR agonists, dexmedetomidine consists of an imidazole ring and a substituted benzene moiety lacking polar groups, which is in contrast to betaAR-selective agonists, which share an ethanolamine group and an aromatic system with polar, hydrogen-bonding substituents. To better understand the structural basis for the selectivity and efficacy of adrenergic agonists, we determined the structure of the alpha2BAR in complex with dexmedetomidine and Go at a resolution of 2.9 A by single-particle cryo-EM. The structure reveals the mechanism of alpha2AR-selective activation and provides insights into Gi/o coupling specificity.
Activation of the alpha2B adrenoceptor by the sedative sympatholytic dexmedetomidine.,Yuan D, Liu Z, Kaindl J, Maeda S, Zhao J, Sun X, Xu J, Gmeiner P, Wang HW, Kobilka BK Nat Chem Biol. 2020 Mar 9. pii: 10.1038/s41589-020-0492-2. doi:, 10.1038/s41589-020-0492-2. PMID:32152538[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yuan D, Liu Z, Kaindl J, Maeda S, Zhao J, Sun X, Xu J, Gmeiner P, Wang HW, Kobilka BK. Activation of the alpha2B adrenoceptor by the sedative sympatholytic dexmedetomidine. Nat Chem Biol. 2020 Mar 9. pii: 10.1038/s41589-020-0492-2. doi:, 10.1038/s41589-020-0492-2. PMID:32152538 doi:http://dx.doi.org/10.1038/s41589-020-0492-2
