|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6i0q' size='340' side='right'caption='[[6i0q]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='6i0q' size='340' side='right'caption='[[6i0q]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6i0q]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I0Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I0Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6i0q]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I0Q FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KCTD16, KIAA1317 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.3Å</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=6i0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i0q OCA], [http://pdbe.org/6i0q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i0q RCSB], [http://www.ebi.ac.uk/pdbsum/6i0q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i0q 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=6i0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i0q OCA], [https://pdbe.org/6i0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i0q RCSB], [https://www.ebi.ac.uk/pdbsum/6i0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i0q ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KCD16_HUMAN KCD16_HUMAN]] Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization (By similarity). | + | [https://www.uniprot.org/uniprot/KCD16_HUMAN KCD16_HUMAN] Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kasaragod, V B]] | + | [[Category: Kasaragod VB]] |
| - | [[Category: Schindelin, H]] | + | [[Category: Schindelin H]] |
| - | [[Category: Sereikaite, V]] | + | [[Category: Sereikaite V]] |
| - | [[Category: Stromgaard, K]] | + | [[Category: Stromgaard K]] |
| - | [[Category: Kctd]]
| + | |
| - | [[Category: Receptor associated protein]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| Structural highlights
Function
KCD16_HUMAN Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization (By similarity).
Publication Abstract from PubMed
Targeting multiprotein receptor complexes, rather than receptors directly, is a promising concept in drug discovery. This is particularly relevant to the GABAB receptor complex, which plays a prominent role in many brain functions and diseases. Here, we provide the first studies targeting a key protein-protein interaction of the GABAB receptor complex-the interaction with KCTD proteins. By employing the muSPOT technology, we first defined the GABAB receptor-binding epitope mediating the KCTD interaction. Subsequently, we developed a highly potent peptide-based inhibitor that interferes with the KCTD/GABAB receptor complex and efficiently isolates endogenous KCTD proteins from mouse brain lysates. X-ray crystallography and SEC-MALS revealed inhibitor induced oligomerization of KCTD16 into a distinct hexameric structure. Thus, we provide a template for modulating the GABAB receptor complex, revealing a fundamentally novel approach for targeting GABAB receptor-associated neuropsychiatric disorders.
Targeting the gamma-Aminobutyric Acid Type B (GABAB) Receptor Complex: Development of Inhibitors Targeting the K(+) Channel Tetramerization Domain (KCTD) Containing Proteins/GABAB Receptor Protein-Protein Interaction.,Sereikaite V, Fritzius T, Kasaragod VB, Bader N, Maric HM, Schindelin H, Bettler B, Stromgaard K J Med Chem. 2019 Sep 25. doi: 10.1021/acs.jmedchem.9b01087. PMID:31509708[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sereikaite V, Fritzius T, Kasaragod VB, Bader N, Maric HM, Schindelin H, Bettler B, Stromgaard K. Targeting the gamma-Aminobutyric Acid Type B (GABAB) Receptor Complex: Development of Inhibitors Targeting the K(+) Channel Tetramerization Domain (KCTD) Containing Proteins/GABAB Receptor Protein-Protein Interaction. J Med Chem. 2019 Sep 25. doi: 10.1021/acs.jmedchem.9b01087. PMID:31509708 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01087
|
