3zrt

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human PSD-95 PDZ1-2

Structural highlights

3zrt is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.398Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).

Publication Abstract from PubMed

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.

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^[1]

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

References

↑ 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. A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage. Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3317-22. Epub 2012 Feb 17. PMID:22343531 doi:10.1073/pnas.1113761109

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Homo sapiens | Large Structures | Gajhede M | Kastrup JS | Sorensen PL

@@ Line 3: / Line 3: @@
 <StructureSection load='3zrt' size='340' side='right'caption='[[3zrt]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3zrt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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>
+<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>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1kef|1kef]]</div></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]] 3.398&#8491;</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=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>
 </table>
 == Function ==
-[[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).
+[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).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Gajhede, M]]
+[[Category: Gajhede M]]
-[[Category: Kastrup, J S]]
+[[Category: Kastrup JS]]
-[[Category: Sorensen, P L]]
+[[Category: Sorensen PL]]
-[[Category: Signaling protein]]

3zrt

From Proteopedia

Current revision

Crystal structure of human PSD-95 PDZ1-2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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