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9IK9

Cryo-EM Structure of SST analogs bond SSTR1-Gi complex

Summary for 9IK9
Entry DOI10.2210/pdb9ik9/pdb
EMDB information60651
DescriptorGuanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
Functional Keywordssstr1, sst analogs, membrane protein
Biological sourceHomo sapiens (human)
More
Total number of polymer chains6
Total formula weight169618.23
Authors
Wong, T.S.,Zeng, Z.C.,Xiong, T.T.,Gan, S.Y.,Du, Y. (deposition date: 2024-06-26, release date: 2025-04-30, Last modification date: 2025-06-25)
Primary citationZeng, Z.,Liao, Q.,Gan, S.,Li, X.,Xiong, T.,Xu, L.,Li, D.,Jiang, Y.,Chen, J.,Ye, R.,Du, Y.,Wong, T.
Structural insights into the binding modes of lanreotide and pasireotide with somatostatin receptor 1.
Acta Pharm Sin B, 15:2468-2479, 2025
Cited by
PubMed Abstract: Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.
PubMed: 40487642
DOI: 10.1016/j.apsb.2025.03.043
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.37 Å)
Structure validation

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