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| | <StructureSection load='4u91' size='340' side='right'caption='[[4u91]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='4u91' size='340' side='right'caption='[[4u91]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4u91]] is a 3 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=4U91 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U91 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4u91]] 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=4U91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U91 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3F7:1,1-BENZENE-1,4-DIYLBIS(1H-PYRROLE-2,5-DIONE)'>3F7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3F7:1,1-BENZENE-1,4-DIYLBIS(1H-PYRROLE-2,5-DIONE)'>3F7</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u90|4u90]], [[4pd0|4pd0]], [[4pd1|4pd1]], [[4tk1|4tk1]], [[4tk2|4tk2]], [[4tk3|4tk3]], [[4tk4|4tk4]]</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=4u91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u91 OCA], [https://pdbe.org/4u91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u91 RCSB], [https://www.ebi.ac.uk/pdbsum/4u91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u91 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gphn, Gph ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u91 OCA], [http://pdbe.org/4u91 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u91 RCSB], [http://www.ebi.ac.uk/pdbsum/4u91 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u91 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> | + | [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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kasaragod, V B]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Maric, H M]] | + | [[Category: Kasaragod VB]] |
| - | [[Category: Schindelin, H]] | + | [[Category: Maric HM]] |
| - | [[Category: Gaba type a receptor]] | + | [[Category: Schindelin H]] |
| - | [[Category: Inhibitory synapse]]
| + | |
| - | [[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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