7p0f
From Proteopedia
(Difference between revisions)
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==Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor HTL0028125== | ==Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor HTL0028125== | ||
| - | <StructureSection load='7p0f' size='340' side='right'caption='[[7p0f]]' scene=''> | + | <StructureSection load='7p0f' size='340' side='right'caption='[[7p0f]], [[Resolution|resolution]] 1.85Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P0F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7p0f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7P0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P0F FirstGlance]. <br> |
| - | </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=7p0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p0f OCA], [https://pdbe.org/7p0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p0f RCSB], [https://www.ebi.ac.uk/pdbsum/7p0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p0f ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7IR:(1S,10R,23E)-12-methyl-10-[(7-methyl-1H-indazol-5-yl)methyl]-15,18,21-trioxa-5,9,12,27,29-pentazapentacyclo[23.5.2.11,4.13,7.028,31]tetratriaconta-3(33),4,6,23,25(32),26,28(31)-heptaene-8,11,30-trione'>7IR</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</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=7p0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p0f OCA], [https://pdbe.org/7p0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p0f RCSB], [https://www.ebi.ac.uk/pdbsum/7p0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p0f ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.[https://www.uniprot.org/uniprot/RAMP1_HUMAN RAMP1_HUMAN] Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for calcitonin-gene-related peptide (CGRP) together with CALCRL.<ref>PMID:9620797</ref> [https://www.uniprot.org/uniprot/CALRL_HUMAN CALRL_HUMAN] Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.<ref>PMID:22102369</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A series of macrocyclic calcitonin gene-related peptide (CGRP) receptor antagonists identified using structure-based design principles, exemplified by HTL0028016 (1) and HTL0028125 (2), is described. Structural characterization by X-ray crystallography of the interaction of two of the macrocycle antagonists with the CGRP receptor ectodomain is described, along with structure-activity relationships associated with point changes to the macrocyclic antagonists. The identification of non-peptidic/natural product-derived, macrocyclic ligands for a G protein coupled receptor (GPCR) is noteworthy. | ||
| + | |||
| + | Novel Macrocyclic Antagonists of the Calcitonin Gene-Related Peptide Receptor: Design, Realization, and Structural Characterization of Protein-Ligand Complexes.,Cansfield AD, Ator MA, Banerjee J, Bestwick M, Bortolato A, Brown GA, Brown J, Butkovic K, Cansfield JE, Christopher JA, Congreve M, Cseke G, Deflorian F, Dugan B, Hunjadi MP, Hutinec A, Inturi TK, Landek G, Mason J, O'Brien A, Ott GR, Rupcic R, Saxty G, Southall SM, Zadravec R, Watson SP ACS Chem Neurosci. 2022 Mar 16;13(6):751-765. doi: 10.1021/acschemneuro.1c00696. , Epub 2022 Mar 4. PMID:35245037<ref>PMID:35245037</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7p0f" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Maltose-binding protein 3D structures|Maltose-binding protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Escherichia coli K-12]] | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Southall SM]] | [[Category: Southall SM]] | ||
[[Category: Watson SP]] | [[Category: Watson SP]] | ||
Revision as of 12:59, 1 February 2024
Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor HTL0028125
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