4igt: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4igt]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IGT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IGT FirstGlance]. <br> | <table><tr><td colspan='2'>[[4igt]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IGT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IGT FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3ZA:(4R)-4-{3-[HYDROXY(METHYL)AMINO]-3-OXOPROPYL}-L-GLUTAMIC+ACID'>3ZA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LI:LITHIUM+ION'>LI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3ZA:(4R)-4-{3-[HYDROXY(METHYL)AMINO]-3-OXOPROPYL}-L-GLUTAMIC+ACID'>3ZA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LI:LITHIUM+ION'>LI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Glur2, Gria2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Glur2, Gria2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4igt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4igt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4igt RCSB], [http://www.ebi.ac.uk/pdbsum/4igt 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=4igt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4igt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4igt RCSB], [http://www.ebi.ac.uk/pdbsum/4igt PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT]] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. 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. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 25: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Buffalo rat]] | [[Category: Buffalo rat]] | ||
[[Category: Frydenvang, K | [[Category: Frydenvang, K]] | ||
[[Category: Gajhede, M | [[Category: Gajhede, M]] | ||
[[Category: Kastrup, J S | [[Category: Kastrup, J S]] | ||
[[Category: Larsen, A P | [[Category: Larsen, A P]] | ||
[[Category: Venskutonyte, R | [[Category: Venskutonyte, R]] | ||
[[Category: Agonist]] | [[Category: Agonist]] | ||
[[Category: Ampa receptor ligand-binding domain]] | [[Category: Ampa receptor ligand-binding domain]] | ||
[[Category: Glur2-s1s2j]] | [[Category: Glur2-s1s2j]] | ||
[[Category: Membrane protein]] | [[Category: Membrane protein]] | ||
Revision as of 07:47, 25 December 2014
Crystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with the agonist ZA302 at 1.24A resolutionCrystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with the agonist ZA302 at 1.24A resolution
Structural highlights
Function[GRIA2_RAT] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. 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. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Publication Abstract from PubMedIn the mammalian central nervous system, (S)-glutamate (Glu) is released from the presynaptic neuron where it activates a plethora of pre- and postsynaptic Glu receptors. The fast acting ionotropic Glu receptors (iGluRs) are ligand gated ion channels and are believed to be involved in a vast number of neurological functions such as memory and learning, synaptic plasticity, and motor function. The synthesis of 14 enantiopure 2,4-syn-Glu analogues 2b-p is accessed by a short and efficient chemoenzymatic approach starting from readily available cyclohexanone 3. Pharmacological characterization at the iGluRs and EAAT1-3 subtypes revealed analogue 2i as a selective GluK1 ligand with low nanomolar affinity. Two X-ray crystal structures of the key analogue 2i in the ligand-binding domain (LBD) of GluA2 and GluK3 were determined. Partial domain closure was seen in the GluA2-LBD complex with 2i comparable to that induced by kainate. In contrast, full domain closure was observed in the GluK3-LBD complex with 2i, similar to that of GluK3-LBD with glutamate bound. Chemoenzymatic Synthesis of New 2,4-syn-Functionalized (S)-Glutamate Analogues and Structure-Activity Relationship Studies at Ionotropic Glutamate Receptors and Excitatory Amino Acid Transporters.,Assaf Z, Larsen AP, Venskutonyte R, Han L, Abrahamsen B, Nielsen B, Gajhede M, Kastrup JS, Jensen AA, Pickering DS, Frydenvang K, Gefflaut T, Bunch L J Med Chem. 2013 Feb 15. PMID:23414088[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||