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| | ==Human Sulfotranferase SULT1C2 in complex with PAP and pentachlorophenol== | | ==Human Sulfotranferase SULT1C2 in complex with PAP and pentachlorophenol== |
| - | <StructureSection load='2gwh' size='340' side='right' caption='[[2gwh]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='2gwh' size='340' side='right'caption='[[2gwh]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2gwh]] 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=2GWH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GWH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2gwh]] 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=2GWH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GWH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A3P:ADENOSINE-3-5-DIPHOSPHATE'>A3P</scene>, <scene name='pdbligand=PCI:PENTACHLOROPHENOL'>PCI</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ad1|2ad1]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A3P:ADENOSINE-3-5-DIPHOSPHATE'>A3P</scene>, <scene name='pdbligand=PCI:PENTACHLOROPHENOL'>PCI</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SULT1C2 ([http://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=2gwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gwh OCA], [https://pdbe.org/2gwh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gwh RCSB], [https://www.ebi.ac.uk/pdbsum/2gwh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gwh ProSAT]</span></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=2gwh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gwh OCA], [http://pdbe.org/2gwh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gwh RCSB], [http://www.ebi.ac.uk/pdbsum/2gwh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2gwh ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ST1C2_HUMAN ST1C2_HUMAN]] Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of drugs, xenobiotic compounds, hormones, and neurotransmitters. May be involved in the activation of carcinogenic hyroxylamines. Shows activity towards p-nitrophenol and N-hydroxy-2-acetylamino-fluorene (N-OH-2AAF). | + | [https://www.uniprot.org/uniprot/ST1C4_HUMAN ST1C4_HUMAN] Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of phenolic compounds. Can also sulfonate estrogenic compounds, however, the dietary flavonoids (phytoestrogen) and environmental estrogens, like bisphenol A are better substrates than 17beta-estradiol (E2) (PubMed:17425406, PubMed:26948952, PubMed:28222028, PubMed:9852044). Mediates the sulfation of doxorubicin and its analog epirubicin, two antitumor anthracyclines (PubMed:26948952).<ref>PMID:17425406</ref> <ref>PMID:26948952</ref> <ref>PMID:28222028</ref> <ref>PMID:9852044</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gw/2gwh_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gw/2gwh_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2gwh" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2gwh" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Sulfotransferase 3D structures|Sulfotransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Allali-Hassani, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Allali-Hassani A]] |
| - | [[Category: Bochkarev, A]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Dombrovski, L]] | + | [[Category: Bochkarev A]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Dombrovski L]] |
| - | [[Category: Loppnau, P]] | + | [[Category: Edwards AM]] |
| - | [[Category: Pan, P W]] | + | [[Category: Loppnau P]] |
| - | [[Category: Plotnikov, A N]] | + | [[Category: Pan PW]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Plotnikov AN]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Sundstrom M]] |
| - | [[Category: Tempel, W]] | + | [[Category: Tempel W]] |
| - | [[Category: Vedadi, M]] | + | [[Category: Vedadi M]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Weigelt J]] |
| - | [[Category: Pap]]
| + | |
| - | [[Category: Pentachlorophenol]]
| + | |
| - | [[Category: Pesticide]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Sulfate conjugation]]
| + | |
| - | [[Category: Sulfotransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
ST1C4_HUMAN Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of phenolic compounds. Can also sulfonate estrogenic compounds, however, the dietary flavonoids (phytoestrogen) and environmental estrogens, like bisphenol A are better substrates than 17beta-estradiol (E2) (PubMed:17425406, PubMed:26948952, PubMed:28222028, PubMed:9852044). Mediates the sulfation of doxorubicin and its analog epirubicin, two antitumor anthracyclines (PubMed:26948952).[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The human cytosolic sulfotransfases (hSULTs) comprise a family of 12 phase II enzymes involved in the metabolism of drugs and hormones, the bioactivation of carcinogens, and the detoxification of xenobiotics. Knowledge of the structural and mechanistic basis of substrate specificity and activity is crucial for understanding steroid and hormone metabolism, drug sensitivity, pharmacogenomics, and response to environmental toxins. We have determined the crystal structures of five hSULTs for which structural information was lacking, and screened nine of the 12 hSULTs for binding and activity toward a panel of potential substrates and inhibitors, revealing unique "chemical fingerprints" for each protein. The family-wide analysis of the screening and structural data provides a comprehensive, high-level view of the determinants of substrate binding, the mechanisms of inhibition by substrates and environmental toxins, and the functions of the orphan family members SULT1C3 and SULT4A1. Evidence is provided for structural "priming" of the enzyme active site by cofactor binding, which influences the spectrum of small molecules that can bind to each enzyme. The data help explain substrate promiscuity in this family and, at the same time, reveal new similarities between hSULT family members that were previously unrecognized by sequence or structure comparison alone.
Structural and chemical profiling of the human cytosolic sulfotransferases.,Allali-Hassani A, Pan PW, Dombrovski L, Najmanovich R, Tempel W, Dong A, Loppnau P, Martin F, Thornton J, Edwards AM, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH PLoS Biol. 2007 May;5(5):e97. PMID:17425406[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Allali-Hassani A, Pan PW, Dombrovski L, Najmanovich R, Tempel W, Dong A, Loppnau P, Martin F, Thornton J, Edwards AM, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH. Structural and chemical profiling of the human cytosolic sulfotransferases. PLoS Biol. 2007 May;5(5):e97. PMID:17425406 doi:10.1371/journal.pbio.0050097
- ↑ Luo L, Zhou C, Hui Y, Kurogi K, Sakakibara Y, Suiko M, Liu MC. Human cytosolic sulfotransferase SULT1C4 mediates the sulfation of doxorubicin and epirubicin. Drug Metab Pharmacokinet. 2016 Apr;31(2):163-6. PMID:26948952 doi:10.1016/j.dmpk.2016.01.003
- ↑ Guidry AL, Tibbs ZE, Runge-Morris M, Falany CN. Expression, purification and characterization of human cytosolic sulfotransferase (SULT) 1C4. Horm Mol Biol Clin Investig. 2017 Jan 1;29(1):27-36. PMID:28222028 doi:10.1515/hmbci-2016-0053
- ↑ Sakakibara Y, Yanagisawa K, Katafuchi J, Ringer DP, Takami Y, Nakayama T, Suiko M, Liu MC. Molecular cloning, expression, and characterization of novel human SULT1C sulfotransferases that catalyze the sulfonation of N-hydroxy-2-acetylaminofluorene. J Biol Chem. 1998 Dec 18;273(51):33929-35. PMID:9852044 doi:10.1074/jbc.273.51.33929
- ↑ Allali-Hassani A, Pan PW, Dombrovski L, Najmanovich R, Tempel W, Dong A, Loppnau P, Martin F, Thornton J, Edwards AM, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH. Structural and chemical profiling of the human cytosolic sulfotransferases. PLoS Biol. 2007 May;5(5):e97. PMID:17425406 doi:10.1371/journal.pbio.0050097
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