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| | ==GephE in complex with PEG crosslinked GABA receptor alpha3 subunit derived dimeric peptide== | | ==GephE in complex with PEG crosslinked GABA receptor alpha3 subunit derived dimeric peptide== |
| - | <StructureSection load='4u90' size='340' side='right' caption='[[4u90]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4u90' size='340' side='right'caption='[[4u90]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4u90]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U90 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U90 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4u90]] 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=4U90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U90 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3F8:1,1-[ETHANE-1,2-DIYLBIS(OXYETHANE-2,1-DIYL)]BIS(1H-PYRROLE-2,5-DIONE)'>3F8</scene>, <scene name='pdbligand=BU1:1,4-BUTANEDIOL'>BU1</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u91|4u91]], [[4pd0|4pd0]], [[4pd1|4pd1]], [[4tk1|4tk1]], [[4tk2|4tk2]], [[4tk3|4tk3]], [[4tk4|4tk4]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3F8:1,1-[ETHANE-1,2-DIYLBIS(OXYETHANE-2,1-DIYL)]BIS(1H-PYRROLE-2,5-DIONE)'>3F8</scene>, <scene name='pdbligand=BU1:1,4-BUTANEDIOL'>BU1</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=4u90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u90 OCA], [http://pdbe.org/4u90 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u90 RCSB], [http://www.ebi.ac.uk/pdbsum/4u90 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u90 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=4u90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u90 OCA], [https://pdbe.org/4u90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u90 RCSB], [https://www.ebi.ac.uk/pdbsum/4u90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u90 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GEPH_RAT GEPH_RAT]] Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.<ref>PMID:8264797</ref> <ref>PMID:9990024</ref> [[http://www.uniprot.org/uniprot/GBRA3_RAT GBRA3_RAT]] GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. | + | [https://www.uniprot.org/uniprot/GEPH_RAT GEPH_RAT] Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.<ref>PMID:8264797</ref> <ref>PMID:9990024</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4u90" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4u90" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Gephyrin|Gephyrin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Kasaragod, V B]] | + | [[Category: Large Structures]] |
| - | [[Category: Maric, H M]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Schindelin, H]] | + | [[Category: Kasaragod VB]] |
| - | [[Category: Gaba type a receptor]] | + | [[Category: Maric HM]] |
| - | [[Category: Inhibitory synapse]] | + | [[Category: Schindelin H]] |
| - | [[Category: Scaffolding protein]]
| + | |
| - | [[Category: Transfer protein - structural protein complex]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
GEPH_RAT Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.[1] [2]
Publication Abstract from PubMed
Gephyrin is the central scaffolding protein for inhibitory neurotransmitter receptors in the brain. Here we describe the development of dimeric peptides that inhibit the interaction between gephyrin and these receptors, a process which is fundamental to numerous synaptic functions and diseases of the brain. We first identified receptor-derived minimal gephyrin-binding peptides that displayed exclusive binding towards native gephyrin from brain lysates. We then designed and synthesized a series of dimeric ligands, which led to a remarkable 1220-fold enhancement of the gephyrin affinity (KD =6.8 nM). In X-ray crystal structures we visualized the simultaneous dimer-to-dimer binding in atomic detail, revealing compound-specific binding modes. Thus, we defined the molecular basis of the affinity-enhancing effect of multivalent gephyrin inhibitors and provide conceptually novel compounds with therapeutic potential, which will allow further elucidation of the gephyrin-receptor interplay.
Design and Synthesis of High-Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors.,Maric HM, Kasaragod VB, Haugaard-Kedstrom L, Hausrat TJ, Kneussel M, Schindelin H, Stromgaard K Angew Chem Int Ed Engl. 2014 Nov 20. doi: 10.1002/anie.201409043. PMID:25413248[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kirsch J, Wolters I, Triller A, Betz H. Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons. Nature. 1993 Dec 23-30;366(6457):745-8. PMID:8264797 doi:http://dx.doi.org/10.1038/366745a0
- ↑ Stallmeyer B, Schwarz G, Schulze J, Nerlich A, Reiss J, Kirsch J, Mendel RR. The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1333-8. PMID:9990024
- ↑ Maric HM, Kasaragod VB, Haugaard-Kedstrom L, Hausrat TJ, Kneussel M, Schindelin H, Stromgaard K. Design and Synthesis of High-Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors. Angew Chem Int Ed Engl. 2014 Nov 20. doi: 10.1002/anie.201409043. PMID:25413248 doi:http://dx.doi.org/10.1002/anie.201409043
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