1mxx

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(New page: 200px<br /><applet load="1mxx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mxx, resolution 2.00&Aring;" /> '''crystal titration ex...)
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[[Image:1mxx.gif|left|200px]]<br /><applet load="1mxx" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1mxx, resolution 2.00&Aring;" />
 
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'''crystal titration experiments (AMPA co-crystals soaked in 100 uM BrW)'''<br />
 
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==Overview==
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==crystal titration experiments (AMPA co-crystals soaked in 100 uM BrW)==
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Numerous naturally occurring and synthetic alpha-amino acids act as, agonists on (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazole) propionic acid, (AMPA) receptors but nevertheless display significant differences in their, functional properties and modes of interaction. The 5-substituted, willardiines are a series of compounds that exhibit a range of affinities, act as partial agonists, and give rise to intermediate levels of, activation and desensitization. However, the molecular basis for the, activities of 5-substituted willardiines has not been conclusively, elaborated at the level of atomic resolution. Here we provide insight into, the molecular basis of the potency and efficacy elicited by the, 5-substituted willardiines on the basis of cocrystal structures with the, GluR2 ligand-binding core. We also show that the crystallized, ligand-binding core has an affinity for agonists similar to the, ligand-binding core in solution. Analysis of multiple crystal lattices, suggests modes by which the ligand-binding core dimers interact in the, tetrameric receptor. These studies further our understanding of how subtle, differences in the structures of agonists are correlated to changes in the, conformation of residues and water molecules in the immediate binding, pocket and to the degree of domain closure.
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<StructureSection load='1mxx' size='340' side='right'caption='[[1mxx]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1mxx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MXX FirstGlance]. <br>
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</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&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mxx OCA], [https://pdbe.org/1mxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mxx RCSB], [https://www.ebi.ac.uk/pdbsum/1mxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mxx ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mx/1mxx_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mxx ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1MXX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MXX OCA].
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*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
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== References ==
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==Reference==
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<references/>
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Probing the function, conformational plasticity, and dimer-dimer contacts of the GluR2 ligand-binding core: studies of 5-substituted willardiines and GluR2 S1S2 in the crystal., Jin R, Gouaux E, Biochemistry. 2003 May 13;42(18):5201-13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12731861 12731861]
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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[[Category: Gouaux E]]
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[[Category: Gouaux, E.]]
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[[Category: Jin R]]
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[[Category: Jin, R.]]
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[[Category: ZN]]
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[[Category: ampa]]
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[[Category: bromo-willardiine]]
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[[Category: crystal titration]]
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[[Category: glur2]]
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[[Category: ionotropic glutamate receptor]]
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[[Category: ligand binding core]]
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[[Category: partial agonist]]
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[[Category: s1s2]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:47:43 2007''
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Current revision

crystal titration experiments (AMPA co-crystals soaked in 100 uM BrW)

PDB ID 1mxx

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