View source for 8ax7


==Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor HTL0031448==
<StructureSection load='8ax7' size='340' side='right'caption='[[8ax7]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ax7]] 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=8AX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AX7 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=OL0:(1~{S},10~{R},20~{E})-10-[(1,7-dimethylindazol-5-yl)methyl]-12-methyl-15,18-dioxa-9,12,24,26-tetrazapentacyclo[20.5.2.1^{1,4}.1^{3,7}.0^{25,28}]hentriaconta-3(30),4,6,20,22,24,28-heptaene-8,11,27-trione'>OL0</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=8ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ax7 OCA], [https://pdbe.org/8ax7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ax7 RCSB], [https://www.ebi.ac.uk/pdbsum/8ax7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ax7 ProSAT]</span></td></tr>
</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 ==
The diastereomeric macrocyclic calcitonin gene-related peptide (CGRP) antagonists HTL0029881 (3) and HTL0029882 (4), in which the stereochemistry of a spiro center is reversed, surprisingly demonstrate comparable potency. X-ray crystallographic characterization demonstrates that 3 binds to the CGRP receptor in a precedented manner but that 4 binds in an unprecedented, unexpected, and radically different manner. The observation of this phenomenon is noteworthy and may open novel avenues for CGRP receptor antagonist design.

Novel Macrocyclic Antagonists of the CGRP Receptor Part 2: Stereochemical Inversion Induces an Unprecedented Binding Mode.,Southall SM, Banerjee J, Brown J, Butkovic K, Cansfield AD, Cansfield JE, Congreve MS, Cseke G, Deflorian F, Hunjadi MP, Hutinec A, Inturi TK, Rupcic R, Saxty G, Watson SP ACS Med Chem Lett. 2022 Oct 19;13(11):1776-1782. doi: , 10.1021/acsmedchemlett.2c00400. eCollection 2022 Nov 10. PMID:36385934<ref>PMID:36385934</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ax7" style="background-color:#fffaf0;"></div>

==See Also==
*[[Maltose-binding protein 3D structures|Maltose-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Southall SM]]
[[Category: Watson SP]]