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| | <StructureSection load='5emt' size='340' side='right'caption='[[5emt]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='5emt' size='340' side='right'caption='[[5emt]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5emt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EMT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EMT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5emt]] 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=5EMT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EMT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</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]] 1.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tw2|3tw2]], [[1kpa|1kpa]], [[1kpb|1kpb]], [[1kpc|1kpc]], [[1kpe|1kpe]], [[1av5|1av5]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5emt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5emt OCA], [http://pdbe.org/5emt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5emt RCSB], [http://www.ebi.ac.uk/pdbsum/5emt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5emt 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=5emt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5emt OCA], [https://pdbe.org/5emt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5emt RCSB], [https://www.ebi.ac.uk/pdbsum/5emt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5emt 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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Finzel, B C]] | + | [[Category: Finzel BC]] |
| - | [[Category: Maize, K M]] | + | [[Category: Maize KM]] |
| - | [[Category: Nix, J C]] | + | [[Category: Nix JC]] |
| - | [[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
Human histidine triad nucleotide binding protein 1 (hHint1) is a purine nucleoside phosphoramidase and adenylate hydrolase that has emerged as a potential therapeutic target for the management of pain. However, the molecular mechanism of Hint1 in the signaling pathway has remained less clear. The role of metal ions in regulating postsynaptic transmission is well known, and the active site of hHint1 contains multiple histidines. Here we have investigated the effect of divalent metal ions (Cd2+, Cu2+, Mg2+, Mn2+, Ni2+, and Zn2+) on the structural integrity and catalytic activity of hHint1. With the exception of Mg2+, all the divalent ions inhibited hHint1, the rank of order was found to be Cu2+ >Zn2+ >Cd2+ >/=Ni2+ >Mn2+ based on their IC50 and kin/KI values. A crystal structure of hHint1 with bound Cu2+ is described to explain the competitive reversible inactivation of hHint1 by divalent cations. All the metal ions exhibited time- and concentration- dependent inhibition, with the rate of inactivation highly dependent on alterations of the C-terminus. With the exception of Cu2+; restoration of inhibition was observed for all the metal ions after treatment with EDTA. Our studies reveal a loss in secondary structure and aggregation of hHint1 upon incubation with 10-fold excess of copper. Thus, hHint1 appears to be structurally sensitive to irreversible inactivation by copper, which may be of neurotoxicological and pharmacological significance.
Inhibition by divalent metal ions of human histidine triad nucleotide binding protein1 (hHint1), a regulator of opioid analgesia and neuropathic pain.,Shah R, Chou TF, Maize KM, Strom A, Finzel BC, Wagner CR Biochem Biophys Res Commun. 2017 Jul 21. pii: S0006-291X(17)31469-9. doi:, 10.1016/j.bbrc.2017.07.111. PMID:28739258[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shah R, Chou TF, Maize KM, Strom A, Finzel BC, Wagner CR. Inhibition by divalent metal ions of human histidine triad nucleotide binding protein1 (hHint1), a regulator of opioid analgesia and neuropathic pain. Biochem Biophys Res Commun. 2017 Jul 21. pii: S0006-291X(17)31469-9. doi:, 10.1016/j.bbrc.2017.07.111. PMID:28739258 doi:http://dx.doi.org/10.1016/j.bbrc.2017.07.111
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