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| | <StructureSection load='6yvp' size='340' side='right'caption='[[6yvp]], [[Resolution|resolution]] 2.77Å' scene=''> | | <StructureSection load='6yvp' size='340' side='right'caption='[[6yvp]], [[Resolution|resolution]] 2.77Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6yvp]] is a 2 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=6YVP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YVP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6yvp]] 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=6YVP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YVP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGP:2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>DGP</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]] 2.77Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6yi0|6yi0]], [[6ypr|6ypr]], [[6ypx|6ypx]], [[6yqd|6yqd]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGP:2-DEOXYGUANOSINE-5-MONOPHOSPHATE'>DGP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HINT2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6yvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yvp OCA], [https://pdbe.org/6yvp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yvp RCSB], [https://www.ebi.ac.uk/pdbsum/6yvp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yvp 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=6yvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yvp OCA], [https://pdbe.org/6yvp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yvp RCSB], [https://www.ebi.ac.uk/pdbsum/6yvp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yvp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/HINT2_HUMAN HINT2_HUMAN]] Hydrolase probably involved in steroid biosynthesis. May play a role in apoptosis. Has adenosine phosphoramidase activity.<ref>PMID:16762638</ref> <ref>PMID:18653718</ref>
| + | [https://www.uniprot.org/uniprot/HINT2_HUMAN HINT2_HUMAN] Hydrolase probably involved in steroid biosynthesis. May play a role in apoptosis. Has adenosine phosphoramidase activity.<ref>PMID:16762638</ref> <ref>PMID:18653718</ref> |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dolot, R D]] | + | [[Category: Dolot RD]] |
| - | [[Category: Krakowiak, A]] | + | [[Category: Krakowiak A]] |
| - | [[Category: Nawrot, B C]] | + | [[Category: Nawrot BC]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Nucleotide binding protein]]
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| Structural highlights
Function
HINT2_HUMAN Hydrolase probably involved in steroid biosynthesis. May play a role in apoptosis. Has adenosine phosphoramidase activity.[1] [2]
Publication Abstract from PubMed
BACKGROUND: Human HINT2 is an important mitochondrial enzyme involved in many processes such as apoptosis and bioenergetics, but its endogenous substrates and the three-dimensional structure of the full-length protein have not been identified yet. METHODS: An HPLC assay was used to test the hydrolytic activity of HINT2 against various adenosine, guanosine, and 2'-deoxyguanosine derivatives containing phosphate bonds of different types and different leaving groups. Data on binding affinity were obtained by microscale thermophoresis (MST). Crystal structures of HINT2, in its apo form and with a dGMP ligand, were resolved to atomic resolution. RESULTS: HINT2 substrate specificity was similar to that of HINT1, but with the major exception of remarkable discrimination against substrates lacking the 2'-hydroxyl group. The biochemical results were consistent with binding affinity measurements. They showed a similar binding strength of AMP and GMP to HINT2, and much weaker binding of dGMP, in contrast to HINT1. A non-hydrolyzable analog of Ap4A (JB419) interacted with both proteins with similar Kd and Ap4A is the signaling molecule that can interact with hHINT1 and regulate the activity of some transcription factors. CONCLUSIONS: Several forms of homo- and heterodimers of different lengths of N-terminally truncated polypeptides resulting from degradation of the full-length protein were described. Ser144 in HINT2 appeared to be functionally equivalent to Ser107 in HINT1 by supporting the protonation of the leaving group in the hydrolytic mechanism of HINT2. SIGNIFICANCE: Our results should be considered in future studies on the natural function of HINT2 and its role in nucleotide prodrug processing.
Biochemical, crystallographic and biophysical characterization of histidine triad nucleotide-binding protein 2 with different ligands including a non-hydrolyzable analog of Ap4A.,Dolot R, Krakowiak A, Kaczmarek R, Wlodarczyk A, Pichlak M, Nawrot B Biochim Biophys Acta Gen Subj. 2021 Nov;1865(11):129968. doi:, 10.1016/j.bbagen.2021.129968. Epub 2021 Jul 27. PMID:34329705[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Martin J, Magnino F, Schmidt K, Piguet AC, Lee JS, Semela D, St-Pierre MV, Ziemiecki A, Cassio D, Brenner C, Thorgeirsson SS, Dufour JF. Hint2, a mitochondrial apoptotic sensitizer down-regulated in hepatocellular carcinoma. Gastroenterology. 2006 Jun;130(7):2179-88. PMID:16762638 doi:10.1053/j.gastro.2006.03.024
- ↑ Lenglet S, Antigny F, Vetterli L, Dufour JF, Rossier MF. Hint2 is expressed in the mitochondria of H295R cells and is involved in steroidogenesis. Endocrinology. 2008 Nov;149(11):5461-9. doi: 10.1210/en.2008-0400. Epub 2008 Jul , 24. PMID:18653718 doi:10.1210/en.2008-0400
- ↑ Dolot R, Krakowiak A, Kaczmarek R, Wlodarczyk A, Pichlak M, Nawrot B. Biochemical, crystallographic and biophysical characterization of histidine triad nucleotide-binding protein 2 with different ligands including a non-hydrolyzable analog of Ap4A. Biochim Biophys Acta Gen Subj. 2021 Nov;1865(11):129968. doi:, 10.1016/j.bbagen.2021.129968. Epub 2021 Jul 27. PMID:34329705 doi:http://dx.doi.org/10.1016/j.bbagen.2021.129968
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