3zrt

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[[Image:3zrt.jpg|left|200px]]
 
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==Crystal structure of human PSD-95 PDZ1-2==
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The line below this paragraph, containing "STRUCTURE_3zrt", creates the "Structure Box" on the page.
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<StructureSection load='3zrt' size='340' side='right'caption='[[3zrt]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3zrt]] is a 4 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=3ZRT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZRT 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]] 3.398&#8491;</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=3zrt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zrt OCA], [https://pdbe.org/3zrt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zrt RCSB], [https://www.ebi.ac.uk/pdbsum/3zrt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zrt ProSAT]</span></td></tr>
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{{STRUCTURE_3zrt| PDB=3zrt | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DLG4_HUMAN DLG4_HUMAN] Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-d-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.
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===Crystal structure of human PSD-95 PDZ1-2===
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A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage.,Bach A, Clausen BH, Moller M, Vestergaard B, Chi CN, Round A, Sorensen PL, Nissen KB, Kastrup JS, Gajhede M, Jemth P, Kristensen AS, Lundstrom P, Lambertsen KL, Stromgaard K Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3317-22. Epub 2012 Feb 17. PMID:22343531<ref>PMID:22343531</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3zrt" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_22343531}}, adds the Publication Abstract to the page
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*[[Postsynaptic density protein 3D structures|Postsynaptic density protein 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 22343531 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_22343531}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[3zrt]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZRT OCA].
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==Reference==
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<ref group="xtra">PMID:022343531</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Gajhede, M.]]
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[[Category: Large Structures]]
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[[Category: Kastrup, J S.]]
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[[Category: Gajhede M]]
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[[Category: Sorensen, P L.]]
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[[Category: Kastrup JS]]
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[[Category: Signaling protein]]
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[[Category: Sorensen PL]]

Current revision

Crystal structure of human PSD-95 PDZ1-2

PDB ID 3zrt

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