View source for 4lex


==Unliganded crystal structure of mAb7==
<StructureSection load='4lex' size='340' side='right'caption='[[4lex]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4lex]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LEX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LEX 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]] 2.02&#8491;</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=4lex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lex OCA], [https://pdbe.org/4lex PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lex RCSB], [https://www.ebi.ac.uk/pdbsum/4lex PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lex ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Elevated glucagon levels and increased hepatic glucagon receptor (GCGR) signaling contribute to hyperglycemia in type 2 diabetes. We have identified a monoclonal antibody that inhibits GCGR, a class-B G-protein coupled receptor (GPCR), through a unique allosteric mechanism. Binding of this antibody to two distinct sites that lie outside the glucagon binding cleft mediate receptor inhibition. One site consists of a patch of residues that are surface exposed on the face of the extracellular domain (ECD) opposite the ligand-binding cleft while the second binding site consists of residues in the alphaA helix of the ECD. A docking model suggests that the antibody does not occlude the ligand-binding cleft. We solved the crystal structure of GCGR ECD containing a naturally occurring G40S mutation and found a shift in the register of the alphaA helix that prevents antibody binding. We also found that alterations in the alphaA helix impact the normal function of GCGR. We present a model for the allosteric inhibition of GCGR by a monoclonal antibody that may form the basis for the development of allosteric modulators for the treatment of diabetes and other class-B GPCR-related diseases.

Inhibitory mechanism of an allosteric antibody targeting the glucagon receptor.,Mukund S, Shang Y, Clarke HJ, Madjidi A, Corn JE, Kates L, Kolumam G, Chiang V, Luis E, Murray J, Zhang Y, Hotzel I, Koth CM, Allan BB J Biol Chem. 2013 Nov 4. PMID:24189067<ref>PMID:24189067</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4lex" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mukund S]]
[[Category: Murray JM]]