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| | <StructureSection load='7eov' size='340' side='right'caption='[[7eov]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='7eov' size='340' side='right'caption='[[7eov]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7eov]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EOV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7eov]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EOV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EOV FirstGlance]. <br> |
| - | </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=CHD:CHOLIC+ACID'>CHD</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]] 2.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sult2a8, 2810007J24Rik ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=CHD:CHOLIC+ACID'>CHD</scene></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=7eov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eov OCA], [https://pdbe.org/7eov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eov RCSB], [https://www.ebi.ac.uk/pdbsum/7eov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eov 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=7eov FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eov OCA], [https://pdbe.org/7eov PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eov RCSB], [https://www.ebi.ac.uk/pdbsum/7eov PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eov ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/ST2A8_MOUSE ST2A8_MOUSE] Hepatic sulfotransferase involved in the maintenance of bile acid homeostasis and energy balance. Catalyzes the transfer of sulfonate group from 3'-phosphoadenylyl sulfate (PAPS) to the 7-alpha hydroxy group of primary bile acids to form 7-monosulfate derivatives in the pathway of bile acid elimination. Displays high catalytic efficiency toward cholate, chenodeoxycholate and their glycine and taurine conjugates.<ref>PMID:28442498</ref> <ref>PMID:29685090</ref> <ref>PMID:33872606</ref> |
| | <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 7eov" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 7eov" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Sulfotransferase 3D structures|Sulfotransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Kakuta, Y]] | + | [[Category: Kakuta Y]] |
| - | [[Category: Nishio, T]] | + | [[Category: Nishio T]] |
| - | [[Category: Teramoto, T]] | + | [[Category: Teramoto T]] |
| - | [[Category: Sulfotransferase sulfation bile acid metabolism]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
ST2A8_MOUSE Hepatic sulfotransferase involved in the maintenance of bile acid homeostasis and energy balance. Catalyzes the transfer of sulfonate group from 3'-phosphoadenylyl sulfate (PAPS) to the 7-alpha hydroxy group of primary bile acids to form 7-monosulfate derivatives in the pathway of bile acid elimination. Displays high catalytic efficiency toward cholate, chenodeoxycholate and their glycine and taurine conjugates.[1] [2] [3]
Publication Abstract from PubMed
Bile acids play essential roles in facilitating the intestinal absorption of lipophilic nutrients as well as regulation of glucose, lipid, and energy homeostasis via activation of some receptors. Bile acids are cytotoxic, and consequently their concentrations are tightly controlled. A critical pathway for bile acid elimination and detoxification is sulfation. The pattern of bile acid sulfation differs by species. Sulfation preferentially occurs at the 3alpha-OH of bile acids in humans, but at the 7alpha-OH in mice. A recent study identified mouse cytosolic sulfotransferase 2A8 (mSULT2A8) as the major hepatic 7alpha-hydroxyl bile acid-sulfating enzyme. To elucidate the 7alpha-OH specific sulfation mechanism of mSULT2A8, instead of 3alpha-OH specific sulfation in humans, we determined a crystal structure of mSULT2A8 in complex with cholic acid, a major bile acid, and 3'-phosphoadenosine-5'-phosphate, the sulfate donor product. Our study shows that bile acid-binding mode of mSULT2A8 and how the enzyme holds the 7alpha-OH group of bile acids at the catalytic center, revealing that the mechanism underlying 7alpha-OH specific sulfation. The structure shows the substrate binds to mSULT2A8 in an orientation perpendicular to that of human 3alpha-hydroxyl bile acid-sulfotransferase (hSULT2A1). The structure of the complex provides new insight into species different bile acid metabolism.
The crystal structure of mouse SULT2A8 reveals the mechanism of 7alpha-hydroxyl, bile acid sulfation.,Teramoto T, Nishio T, Kurogi K, Sakakibara Y, Kakuta Y Biochem Biophys Res Commun. 2021 May 21;562:15-20. doi:, 10.1016/j.bbrc.2021.04.113. PMID:34030040[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Feng L, Yuen YL, Xu J, Liu X, Chan MY, Wang K, Fong WP, Cheung WT, Lee SS. Identification and characterization of a novel PPARα-regulated and 7α-hydroxyl bile acid-preferring cytosolic sulfotransferase mL-STL (Sult2a8). J Lipid Res. 2017 Jun;58(6):1114-1131. PMID:28442498 doi:10.1194/jlr.M074302
- ↑ Shimohira T, Kurogi K, Liu MC, Suiko M, Sakakibara Y. The critical role of His48 in mouse cytosolic sulfotransferase SULT2A8 for the 7α-hydroxyl sulfation of bile acids. Biosci Biotechnol Biochem. 2018 Aug;82(8):1359-1365. PMID:29685090 doi:10.1080/09168451.2018.1464897
- ↑ Wang K, Chan YC, So PK, Liu X, Feng L, Cheung WT, Lee SS, Au SW. Structure of mouse cytosolic sulfotransferase SULT2A8 provides insight into sulfonation of 7α-hydroxyl bile acids. J Lipid Res. 2021;62:100074. PMID:33872606 doi:10.1016/j.jlr.2021.100074
- ↑ Teramoto T, Nishio T, Kurogi K, Sakakibara Y, Kakuta Y. The crystal structure of mouse SULT2A8 reveals the mechanism of 7alpha-hydroxyl, bile acid sulfation. Biochem Biophys Res Commun. 2021 May 21;562:15-20. doi:, 10.1016/j.bbrc.2021.04.113. PMID:34030040 doi:http://dx.doi.org/10.1016/j.bbrc.2021.04.113
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