Structural highlights
7bts is a 2 chain structure with sequence from Escherichia virus T4, Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 3.13Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ADRB1_HUMAN Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity.D9IEF7_BPT4
Publication Abstract from PubMed
Beta adrenergic receptors (betaARs) mediate physiologic responses to the catecholamines epinephrine and norepinephrine released by the sympathetic nervous system. While the hormone epinephrine binds beta1AR and beta2AR with similar affinity, the smaller neurotransmitter norepinephrine is approximately tenfold selective for the beta1AR. To understand the structural basis for this physiologically important selectivity, we solved the crystal structures of the human beta1AR bound to an antagonist carazolol and different agonists including norepinephrine, epinephrine and BI-167107. Structural comparison revealed that the catecholamine-binding pockets are identical between beta1AR and beta2AR, but the extracellular vestibules have different shapes and electrostatic properties. Metadynamics simulations and mutagenesis studies revealed that these differences influence the path norepinephrine takes to the orthosteric pocket and contribute to the different association rates and thus different affinities.
Binding pathway determines norepinephrine selectivity for the human beta1AR over beta2AR.,Xu X, Kaindl J, Clark MJ, Hubner H, Hirata K, Sunahara RK, Gmeiner P, Kobilka BK, Liu X Cell Res. 2020 Oct 22. pii: 10.1038/s41422-020-00424-2. doi:, 10.1038/s41422-020-00424-2. PMID:33093660[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xu X, Kaindl J, Clark MJ, Hubner H, Hirata K, Sunahara RK, Gmeiner P, Kobilka BK, Liu X. Binding pathway determines norepinephrine selectivity for the human beta1AR over beta2AR. Cell Res. 2020 Oct 22. pii: 10.1038/s41422-020-00424-2. doi:, 10.1038/s41422-020-00424-2. PMID:33093660 doi:http://dx.doi.org/10.1038/s41422-020-00424-2
