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4mf3

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Revision as of 11:44, 4 August 2016

Crystal Structure of Human GRIK1 complexed with a 6-(tetrazolyl)aryl decahydroisoquinoline antagonist

Structural highlights

4mf3 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GRIK1_HUMAN] Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.

Publication Abstract from PubMed

We have explored the decahydroisoquinoline scaffold, bearing a phenyl tetrazole, as GluK1 antagonists with potential as oral analgesics. We have established the optimal linker atom between decahydroisoquinoline and phenyl rings and demonstrated an improvement of both the affinity for the GluK1 receptor and the selectivity against the related GluA2 receptor with proper phenyl substitution. In this Letter, we also disclose in vivo data that led to the discovery of LY545694.HCl, a compound with oral efficacy in two persistent pain models.

GluK1 antagonists from 6-(tetrazolyl)phenyl decahydroisoquinoline derivatives: in vitro profile and in vivo analgesic efficacy.,Martinez-Perez JA, Iyengar S, Shannon HE, Bleakman D, Alt A, Clawson DK, Arnold BM, Bell MG, Bleisch TJ, Castano AM, Del Prado M, Dominguez E, Escribano AM, Filla SA, Ho KH, Hudziak KJ, Jones CK, Mateo A, Mathes BM, Mattiuz EL, Ogden AM, Simmons RM, Stack DR, Stratford RE, Winter MA, Wu Z, Ornstein PL Bioorg Med Chem Lett. 2013 Dec 1;23(23):6463-6. doi: 10.1016/j.bmcl.2013.09.045. , Epub 2013 Sep 24. PMID:24140446^[1]

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

References

↑ Martinez-Perez JA, Iyengar S, Shannon HE, Bleakman D, Alt A, Clawson DK, Arnold BM, Bell MG, Bleisch TJ, Castano AM, Del Prado M, Dominguez E, Escribano AM, Filla SA, Ho KH, Hudziak KJ, Jones CK, Mateo A, Mathes BM, Mattiuz EL, Ogden AM, Simmons RM, Stack DR, Stratford RE, Winter MA, Wu Z, Ornstein PL. GluK1 antagonists from 6-(tetrazolyl)phenyl decahydroisoquinoline derivatives: in vitro profile and in vivo analgesic efficacy. Bioorg Med Chem Lett. 2013 Dec 1;23(23):6463-6. doi: 10.1016/j.bmcl.2013.09.045. , Epub 2013 Sep 24. PMID:24140446 doi:http://dx.doi.org/10.1016/j.bmcl.2013.09.045

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/4mf3"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human GRIK1 complexed with a 6-(tetrazolyl)aryl decahydroisoquinoline antagonist==
 <StructureSection load='4mf3' size='340' side='right' caption='[[4mf3]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4mf3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MF3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MF3 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SXI:(3S,4AS,6S,8AR)-6-[3-CHLORO-2-(1H-TETRAZOL-5-YL)PHENOXY]DECAHYDROISOQUINOLINE-3-CARBOXYLIC+ACID'>SXI</scene></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=4mf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mf3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mf3 RCSB], [http://www.ebi.ac.uk/pdbsum/4mf3 PDBsum]</span></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=4mf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mf3 OCA], [http://pdbe.org/4mf3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mf3 RCSB], [http://www.ebi.ac.uk/pdbsum/4mf3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mf3 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4mf3" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4mf3

From Proteopedia

Revision as of 11:44, 4 August 2016

Crystal Structure of Human GRIK1 complexed with a 6-(tetrazolyl)aryl decahydroisoquinoline antagonist

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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