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| | <StructureSection load='6n3v' size='340' side='right'caption='[[6n3v]], [[Resolution|resolution]] 1.45Å' scene=''> | | <StructureSection load='6n3v' size='340' side='right'caption='[[6n3v]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6n3v]] is a 2 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=6N3V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N3V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n3v]] is a 2 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=6N3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6N3V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KB7:5-O-(ethylcarbamoyl)guanosine'>KB7</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]] 1.45Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HINT1, HINT, PKCI1, PRKCNH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KB7:5-O-(ethylcarbamoyl)guanosine'>KB7</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=6n3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n3v OCA], [http://pdbe.org/6n3v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n3v RCSB], [http://www.ebi.ac.uk/pdbsum/6n3v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n3v 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=6n3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n3v OCA], [https://pdbe.org/6n3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6n3v RCSB], [https://www.ebi.ac.uk/pdbsum/6n3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6n3v ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HINT1_HUMAN HINT1_HUMAN]] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity). | + | [https://www.uniprot.org/uniprot/HINT1_HUMAN HINT1_HUMAN] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity). |
| | <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 6n3v" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6n3v" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Histidine triad nucleotide-binding protein 3D structures|Histidine triad nucleotide-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Finzel, B C]] | + | [[Category: Finzel BC]] |
| - | [[Category: Strom, A M]] | + | [[Category: Strom AM]] |
| - | [[Category: Hint]]
| + | |
| - | [[Category: Histidine triad]]
| + | |
| - | [[Category: Hit]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
HINT1_HUMAN Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity).
Publication Abstract from PubMed
The interactions between the mu-opioid (MOR) and N-methyl-d-aspartate receptor (NMDAR) constitute an area of intense investigation because of their contributions to maladaptive neuroplasticity. Recent evidence suggests that their association requires the involvement of histidine triad nucleotide-binding protein (HINT1) with the enzyme's active site being critical in its regulatory role. Since it is known that spinal blockade of NMDA receptors prevents the development of opioid analgesic tolerance, we hypothesized that spinal inhibition of the HINT1 enzyme may similarly inhibit opioid tolerance. To address these questions, we evaluated novel HINT1 active-site inhibitors in two models of NMDAR and MOR interaction, namely, MOR inhibition of spinal NMDA activation and acute endomorphin-2 tolerance. These studies revealed that while the tryptamine carbamate of guanosine inhibitor, TrpGc, blocked both the development of opioid tolerance and the inhibitory effect of opioids on NMDA activation of the NMDA receptor, acyl-sulfamate analogues could only block the latter. Thermodynamic binding and X-ray crystallographic studies suggested that there are key differences between the bound HINT1-inhibitor surfaces that may be responsible for their differential ability to probe the ability of HINT1 to regulate cross talk between the mu-opioid receptor and NMDA receptor in the spinal cord.
Inhibition of HINT1 Modulates Spinal Nociception and NMDA Evoked Behavior in Mice.,Shah RM, Peterson C, Strom A, Dillenburg M, Finzel B, Kitto KF, Fairbanks C, Wilcox G, Wagner CR ACS Chem Neurosci. 2019 Oct 16;10(10):4385-4393. doi:, 10.1021/acschemneuro.9b00432. Epub 2019 Sep 25. PMID:31503445[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shah RM, Peterson C, Strom A, Dillenburg M, Finzel B, Kitto KF, Fairbanks C, Wilcox G, Wagner CR. Inhibition of HINT1 Modulates Spinal Nociception and NMDA Evoked Behavior in Mice. ACS Chem Neurosci. 2019 Oct 16;10(10):4385-4393. doi:, 10.1021/acschemneuro.9b00432. Epub 2019 Sep 25. PMID:31503445 doi:http://dx.doi.org/10.1021/acschemneuro.9b00432
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