8ha0: Difference between revisions
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The entry | ==Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1== | ||
<StructureSection load='8ha0' size='340' side='right'caption='[[8ha0]], [[Resolution|resolution]] 2.62Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8ha0]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HA0 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=8ha0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ha0 OCA], [https://pdbe.org/8ha0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ha0 RCSB], [https://www.ebi.ac.uk/pdbsum/8ha0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ha0 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PTH1R_HUMAN PTH1R_HUMAN] Blomstrand lethal chondrodysplasia;Dental ankylosis;Eiken syndrome;Metaphyseal chondrodysplasia, Jansen type;Enchondromatosis. 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. The disease may be caused by mutations affecting the gene represented in this entry. 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 == | |||
[https://www.uniprot.org/uniprot/PTH1R_HUMAN PTH1R_HUMAN] This is a receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system.<ref>PMID:18611381</ref> <ref>PMID:20172855</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.62 A and 3.25 A, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders. | |||
Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1.,Zhao LH, Yuan QN, Dai AT, He XH, Chen CW, Zhang C, Xu YW, Zhou Y, Wang MW, Yang DH, Xu HE Acta Pharmacol Sin. 2022 Dec 8. doi: 10.1038/s41401-022-01032-z. PMID:36482086<ref>PMID:36482086</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8ha0" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Yuan | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Rattus norvegicus]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Xu HE]] | |||
[[Category: Yuan Q]] | |||
[[Category: Zhao L]] | |||
Revision as of 12:31, 21 December 2022
Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1
Structural highlights
DiseasePTH1R_HUMAN Blomstrand lethal chondrodysplasia;Dental ankylosis;Eiken syndrome;Metaphyseal chondrodysplasia, Jansen type;Enchondromatosis. 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. The disease may be caused by mutations affecting the gene represented in this entry. 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. FunctionPTH1R_HUMAN This is a receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system.[1] [2] Publication Abstract from PubMedParathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.62 A and 3.25 A, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders. Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1.,Zhao LH, Yuan QN, Dai AT, He XH, Chen CW, Zhang C, Xu YW, Zhou Y, Wang MW, Yang DH, Xu HE Acta Pharmacol Sin. 2022 Dec 8. doi: 10.1038/s41401-022-01032-z. PMID:36482086[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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