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6e5v

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Revision as of 07:04, 5 December 2018

human mGlu8 receptor amino terminal domain in complex with (S)-3,4-Dicarboxyphenylglycine (DCPG)

Structural highlights

6e5v is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	GRM8, GPRC1H, MGLUR8 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GRM8_HUMAN] G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.^[1]

Publication Abstract from PubMed

(S)-3,4-dicarboxyphenylglycine (DCPG) was first reported in 2001 as a potent orthosteric agonist with high subtype selectivity for the mGlu8 receptor, but the structural basis for its high selectivity is not well understood. We have solved a co-crystal structure of recombinant human mGlu8 amino terminal domain (ATD) protein bound to (S)-DCPG, which possesses the largest lobe opening angle observed to date among known agonist-bound mGlu ATD crystal structures. The binding conformation of (S)-DCPG observed in the crystal structure is significantly different from that in the homology model built from an L-Glutamate-bound rat mGlu1 ATD crystal structure, which has a smaller lobe opening angle. This highlights the importance of considering various lobe opening angles when modeling mGlu ATD-ligand complex. New homology models of other mGlu receptors based on the (S)-DCPG-bound mGlu8 ATD crystal structure were explored to rationalize (S)-DCPG's high mGlu8 receptor subtype selectivity.

Structural Basis for (S)-3,4-Dicarboxyphenylglycine (DCPG) As a Potent and Subtype Selective Agonist of the mGlu8 Receptor.,Chen Q, Ho JD, Ashok S, Vargas MC, Wang J, Atwell S, Bures M, Schkeryantz JM, Monn JA, Hao J J Med Chem. 2018 Oct 26. doi: 10.1021/acs.jmedchem.8b01120. PMID:30365309^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR Jr, Johnson BG, Schoepp DD, Belagaje RM. Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells. Brain Res Mol Brain Res. 1998 Jan;53(1-2):88-97. PMID:9473604
↑ Chen Q, Ho JD, Ashok S, Vargas MC, Wang J, Atwell S, Bures M, Schkeryantz JM, Monn JA, Hao J. Structural Basis for (S)-3,4-Dicarboxyphenylglycine (DCPG) As a Potent and Subtype Selective Agonist of the mGlu8 Receptor. J Med Chem. 2018 Oct 26. doi: 10.1021/acs.jmedchem.8b01120. PMID:30365309 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01120

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6e5v"

@@ Line 3: / Line 3: @@
 <StructureSection load='6e5v' size='340' side='right' caption='[[6e5v]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6e5v]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E5V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6e5v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E5V FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HVG:4-[(S)-amino(carboxy)methyl]benzene-1,2-dicarboxylic+acid'>HVG</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRM8, GPRC1H, MGLUR8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e5v OCA], [http://pdbe.org/6e5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e5v RCSB], [http://www.ebi.ac.uk/pdbsum/6e5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e5v ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Ashok, S]]
 [[Category: Atwell, S]]

6e5v

From Proteopedia

Revision as of 07:04, 5 December 2018

human mGlu8 receptor amino terminal domain in complex with (S)-3,4-Dicarboxyphenylglycine (DCPG)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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