3m3f

From Proteopedia

(Difference between revisions)

Revision as of 08:47, 6 September 2023

PEPA bound to the ligand binding domain of GluA3 (flop form)

Structural highlights

3m3f is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GRIA3_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 (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Glutamate receptors are important potential drug targets for cognitive enhancement and the treatment of schizophrenia in part because they are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. One approach to the application of therapeutic agents to the AMPA subtype of glutamate receptors is the use of allosteric modulators, which promote dimerization by binding to a dimer interface thereby reducing the degree of desensitization and deactivation. AMPA receptors exist in two alternatively spliced variants (flip and flop) that differ in desensitization and receptor activation profiles. Most of the structural information about modulators of the AMPA receptor targets the flip subtype. We report here the crystal structure of the flop-selective allosteric modulator, PEPA, bound to the binding domains of the GluA2 and GluA3 flop isoforms of AMPA receptors. Specific hydrogen bonding patterns can explain the preference for the flop isoform. This includes a bidentate hydrogen bonding pattern between PEPA and N754 of the flop isoforms of GluA2 and GluA3 (the corresponding position in the flip isoform is S754). Comparison with other allosteric modulators provides a framework for the development of new allosteric modulators with preferences for either the flip or flop isoforms. In addition to interactions with N/S754, specific interactions of the sulfonamide with conserved residues in the binding site are characteristics of a number of allosteric modulators. These, in combination with variable interactions with five subsites on the binding surface, lead to different stoichiometries, orientations within the binding pockets, and functional outcomes.

Molecular Mechanism of Flop Selectivity and Subsite Recognition for an AMPA Receptor Allosteric Modulator: Structures of GluA2 and GluA3 in Complexes with PEPA.,Ahmed AH, Ptak CP, Oswald RE Biochemistry. 2010 Mar 12. PMID:20199107^[1]

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

References

↑ Ahmed AH, Ptak CP, Oswald RE. Molecular Mechanism of Flop Selectivity and Subsite Recognition for an AMPA Receptor Allosteric Modulator: Structures of GluA2 and GluA3 in Complexes with PEPA. Biochemistry. 2010 Mar 12. PMID:20199107 doi:10.1021/bi1000678

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3m3f"

Categories: Large Structures | Rattus norvegicus | Ahmed AH | Oswald RE | Ptak CP

@@ Line 1: / Line 1: @@
 ==PEPA bound to the ligand binding domain of GluA3 (flop form)==
-<StructureSection load='3m3f' size='340' side='right' caption='[[3m3f]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='3m3f' size='340' side='right'caption='[[3m3f]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3m3f]] 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=3M3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3M3F FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3m3f]] is a 1 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=3M3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3M3F FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=P99:2-[2,6-DIFLUORO-4-({2-[(PHENYLSULFONYL)AMINO]ETHYL}SULFANYL)PHENOXY]ACETAMIDE'>P99</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.5&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3m3k|3m3k]], [[3m3l|3m3l]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=P99:2-[2,6-DIFLUORO-4-({2-[(PHENYLSULFONYL)AMINO]ETHYL}SULFANYL)PHENOXY]ACETAMIDE'>P99</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gria3, Glur3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3m3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m3f OCA], [https://pdbe.org/3m3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3m3f RCSB], [https://www.ebi.ac.uk/pdbsum/3m3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3m3f ProSAT]</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=3m3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m3f OCA], [http://pdbe.org/3m3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3m3f RCSB], [http://www.ebi.ac.uk/pdbsum/3m3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3m3f ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GRIA3_RAT GRIA3_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 (By similarity).
+[https://www.uniprot.org/uniprot/GRIA3_RAT GRIA3_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 (By similarity).
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m3/3m3f_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m3/3m3f_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 30: / Line 29: @@
 </div>
 <div class="pdbe-citations 3m3f" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Buffalo rat]]
+[[Category: Large Structures]]
-[[Category: Ahmed, A H]]
+[[Category: Rattus norvegicus]]
-[[Category: Oswald, R E]]
+[[Category: Ahmed AH]]
-[[Category: Ptak, C P]]
+[[Category: Oswald RE]]
-[[Category: Ampa receptor]]
+[[Category: Ptak CP]]
-[[Category: Glua3]]
-[[Category: Glur3]]
-[[Category: Glutamate receptor]]
-[[Category: Neurotransmitter receptor]]
-[[Category: S1s2]]
-[[Category: Transport protein]]

3m3f

From Proteopedia

Revision as of 08:47, 6 September 2023

PEPA bound to the ligand binding domain of GluA3 (flop form)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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