5ewm: Difference between revisions

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 ==CRYSTAL STRUCTURE OF AMINO TERMINAL DOMAINS OF THE NMDA RECEPTOR SUBUNIT GLUN1 AND GLUN2B IN COMPLEX WITH EVT-101==
-<StructureSection load='5ewm' size='340' side='right' caption='[[5ewm]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
+<StructureSection load='5ewm' size='340' side='right'caption='[[5ewm]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ewm]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EWM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EWM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ewm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EWM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EWM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5SM:5-[3-[BIS(FLUORANYL)METHYL]-4-FLUORANYL-PHENYL]-3-[(2-METHYLIMIDAZOL-1-YL)METHYL]PYRIDAZINE'>5SM</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 2.76&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5wmj|5wmj]], [[5wml|5wml]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5SM:5-[3-[BIS(FLUORANYL)METHYL]-4-FLUORANYL-PHENYL]-3-[(2-METHYLIMIDAZOL-1-YL)METHYL]PYRIDAZINE'>5SM</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=5ewm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ewm OCA], [http://pdbe.org/5ewm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ewm RCSB], [http://www.ebi.ac.uk/pdbsum/5ewm PDBsum]</span></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=5ewm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ewm OCA], [https://pdbe.org/5ewm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ewm RCSB], [https://www.ebi.ac.uk/pdbsum/5ewm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ewm ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/NMDE2_HUMAN NMDE2_HUMAN]] Autosomal dominant non-syndromic intellectual disability;West syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  A chromosomal aberrations involving GRIN2B has been found in patients with mental retardation. Translocations t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint in 12p13.1.
+[https://www.uniprot.org/uniprot/NMDE2_HUMAN NMDE2_HUMAN] Autosomal dominant non-syndromic intellectual disability;West syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  A chromosomal aberrations involving GRIN2B has been found in patients with mental retardation. Translocations t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint in 12p13.1.
 == Function ==
-[[http://www.uniprot.org/uniprot/NMDE2_HUMAN NMDE2_HUMAN]] NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity).
+[https://www.uniprot.org/uniprot/NMDE2_HUMAN NMDE2_HUMAN] NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+NMDA receptors (NMDARs) are glutamate-gated ion channels that play key roles in brain physiology and pathology. Because numerous pathological conditions involve NMDAR overactivation, subunit-selective antagonists hold strong therapeutic potential, although clinical successes remain limited. Among the most promising NMDAR-targeting drugs are allosteric inhibitors of GluN2B-containing receptors. Since the discovery of ifenprodil, a range of GluN2B-selective compounds with strikingly different structural motifs have been identified. This molecular diversity raises the possibility of distinct binding sites, although supporting data are lacking. Using x-ray crystallography, we show that EVT-101, a GluN2B antagonist structurally unrelated to the classical phenylethanolamine pharmacophore, binds at the same GluN1/GluN2B dimer interface as ifenprodil but adopts a remarkably different binding mode involving a distinct subcavity and receptor interactions. Mutagenesis experiments demonstrate that this novel binding site is physiologically relevant. Moreover, in silico docking unveils that GluN2B-selective antagonists broadly divide into two distinct classes according to binding pose. These data widen the allosteric and pharmacological landscape of NMDARs and offer a renewed structural framework for designing next-generation GluN2B antagonists with therapeutic value for brain disorders.
+A novel binding mode reveals two distinct classes of NMDA receptor GluN2B-selective antagonists.,Stroebel D, Buhl DL, Knafels JD, Chanda PK, Green M, Sciabola S, Mony L, Paoletti P, Pandit J Mol Pharmacol. 2016 Feb 24. pii: mol.115.103036. PMID:26912815<ref>PMID:26912815</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 5ewm" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
-[[Category: Pandit, J]]
+[[Category: Homo sapiens]]
-[[Category: Allosteric modulator]]
+[[Category: Large Structures]]
-[[Category: Glun2b antagonist]]
+[[Category: Xenopus laevis]]
-[[Category: Glutamate receptor]]
+[[Category: Pandit J]]
-[[Category: Transport protein]]