6e7r: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 3: / Line 3: @@
 <StructureSection load='6e7r' size='340' side='right'caption='[[6e7r]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6e7r]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E7R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E7R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6e7r]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] 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=6E7R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E7R FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HYS:N-{4-[(2S)-3-{[2-(3,4-dichlorophenyl)ethyl]amino}-2-hydroxypropoxy]phenyl}methanesulfonamide'>HYS</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]] 2.1&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">grin1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog]), Grin2b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HYS:N-{4-[(2S)-3-{[2-(3,4-dichlorophenyl)ethyl]amino}-2-hydroxypropoxy]phenyl}methanesulfonamide'>HYS</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=6e7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e7r OCA], [http://pdbe.org/6e7r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e7r RCSB], [http://www.ebi.ac.uk/pdbsum/6e7r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e7r ProSAT]</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=6e7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e7r OCA], [https://pdbe.org/6e7r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e7r RCSB], [https://www.ebi.ac.uk/pdbsum/6e7r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e7r ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NMDZ1_XENLA NMDZ1_XENLA]] Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:16214956, PubMed:19524674, PubMed:21677647, PubMed:25008524, PubMed:26912815, PubMed:27135925, Ref.11, PubMed:28232581). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable).<ref>PMID:16214956</ref> <ref>PMID:19524674</ref> <ref>PMID:21677647</ref> <ref>PMID:25008524</ref> <ref>PMID:26912815</ref> <ref>PMID:27135925</ref> <ref>PMID:28232581</ref> [PDB:5IOV] [[http://www.uniprot.org/uniprot/NMDE2_RAT NMDE2_RAT]] 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/NMDZ1_XENLA NMDZ1_XENLA] Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:16214956, PubMed:19524674, PubMed:21677647, PubMed:25008524, PubMed:26912815, PubMed:27135925, Ref.11, PubMed:28232581). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable).<ref>PMID:16214956</ref> <ref>PMID:19524674</ref> <ref>PMID:21677647</ref> <ref>PMID:25008524</ref> <ref>PMID:26912815</ref> <ref>PMID:27135925</ref> <ref>PMID:28232581</ref> [PDB:5IOV]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Context-dependent inhibition of N-methyl-D-aspartate (NMDA) receptors has important therapeutic implications for the treatment of neurological diseases that are associated with altered neuronal firing and signaling. This is especially true in stroke, where the proton concentration in the afflicted area can increase by an order of magnitude. A class of allosteric inhibitors, the 93-series, shows greater potency against GluN1-GluN2B NMDA receptors in such low pH environments, allowing targeted therapy only within the ischemic region. Here we map the 93-series compound binding site in the GluN1-GluN2B NMDA receptor amino terminal domain and show that the interaction of the N-alkyl group with a hydrophobic cage of the binding site is critical for pH-dependent inhibition. Mutation of residues in the hydrophobic cage alters pH-dependent potency, and remarkably, can convert inhibitors into potentiators. Our study provides a foundation for the development of highly specific neuroprotective compounds for the treatment of neurological diseases.
+Structural elements of a pH-sensitive inhibitor binding site in NMDA receptors.,Regan MC, Zhu Z, Yuan H, Myers SJ, Menaldino DS, Tahirovic YA, Liotta DC, Traynelis SF, Furukawa H Nat Commun. 2019 Jan 18;10(1):321. doi: 10.1038/s41467-019-08291-1. PMID:30659174<ref>PMID:30659174</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6e7r" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 17: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: African clawed frog]]
-[[Category: Buffalo rat]]
 [[Category: Large Structures]]
-[[Category: Furukawa, H]]
+[[Category: Rattus norvegicus]]
-[[Category: Regan, M C]]
+[[Category: Xenopus laevis]]
-[[Category: Allosteric modulation]]
+[[Category: Furukawa H]]
-[[Category: Extracellular domain]]
+[[Category: Regan MC]]
-[[Category: Ion channel]]
-[[Category: Nmda receptor]]
-[[Category: Transport protein]]