7yac: Difference between revisions
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==Paltusotine-bound SSTR2-Gi complex== | |||
<StructureSection load='7yac' size='340' side='right'caption='[[7yac]], [[Resolution|resolution]] 3.24Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7yac]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YAC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YAC FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.24Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IUD:3-[4-(4-azanylpiperidin-1-yl)-3-[3,5-bis(fluoranyl)phenyl]quinolin-6-yl]-2-oxidanyl-benzenecarbonitrile'>IUD</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7yac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yac OCA], [https://pdbe.org/7yac PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yac RCSB], [https://www.ebi.ac.uk/pdbsum/7yac PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yac ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_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.<ref>PMID:18611381</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Somatostatin receptor 2 (SSTR2) is highly expressed in neuroendocrine tumors and represents as a therapeutic target. Several peptide analogs mimicking the endogenous ligand somatostatin are available for clinical use, but poor therapeutic effects occur in a subset of patients, which may be correlated with subtype selectivity or cell surface expression. Here, we clarify the signal bias profiles of the first-generation peptide drug octreotide and a new-generation small molecule paltusotine by evaluating their pharmacological characteristics. We then perform cryo-electron microscopy analysis of SSTR2-Gi complexes to determine how the drugs activate SSTR2 in a selective manner. In this work, we decipher the mechanism of ligand recognition, subtype selectivity and signal bias property of SSTR2 sensing octreotide and paltusotine, which may aid in designing therapeutic drugs with specific pharmacological profiles against neuroendocrine tumors. | |||
Prospect of acromegaly therapy: molecular mechanism of clinical drugs octreotide and paltusotine.,Zhao J, Fu H, Yu J, Hong W, Tian X, Qi J, Sun S, Zhao C, Wu C, Xu Z, Cheng L, Chai R, Yan W, Wei X, Shao Z Nat Commun. 2023 Feb 21;14(1):962. doi: 10.1038/s41467-023-36673-z. PMID:36810324<ref>PMID:36810324</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7yac" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Shao Z]] | |||
[[Category: Zhao J]] | |||
Latest revision as of 14:50, 30 October 2024
Paltusotine-bound SSTR2-Gi complexPaltusotine-bound SSTR2-Gi complex
Structural highlights
FunctionGBB1_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.[1] Publication Abstract from PubMedSomatostatin receptor 2 (SSTR2) is highly expressed in neuroendocrine tumors and represents as a therapeutic target. Several peptide analogs mimicking the endogenous ligand somatostatin are available for clinical use, but poor therapeutic effects occur in a subset of patients, which may be correlated with subtype selectivity or cell surface expression. Here, we clarify the signal bias profiles of the first-generation peptide drug octreotide and a new-generation small molecule paltusotine by evaluating their pharmacological characteristics. We then perform cryo-electron microscopy analysis of SSTR2-Gi complexes to determine how the drugs activate SSTR2 in a selective manner. In this work, we decipher the mechanism of ligand recognition, subtype selectivity and signal bias property of SSTR2 sensing octreotide and paltusotine, which may aid in designing therapeutic drugs with specific pharmacological profiles against neuroendocrine tumors. Prospect of acromegaly therapy: molecular mechanism of clinical drugs octreotide and paltusotine.,Zhao J, Fu H, Yu J, Hong W, Tian X, Qi J, Sun S, Zhao C, Wu C, Xu Z, Cheng L, Chai R, Yan W, Wei X, Shao Z Nat Commun. 2023 Feb 21;14(1):962. doi: 10.1038/s41467-023-36673-z. PMID:36810324[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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