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| - | [[Image:1q22.gif|left|200px]] | |
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| - | {{Structure
| + | ==Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of DHEA and PAP== |
| - | |PDB= 1q22 |SIZE=350|CAPTION= <scene name='initialview01'>1q22</scene>, resolution 2.50Å
| + | <StructureSection load='1q22' size='340' side='right'caption='[[1q22]], [[Resolution|resolution]] 2.50Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=A3P:ADENOSINE-3'-5'-DIPHOSPHATE'>A3P</scene>, <scene name='pdbligand=AND:3-BETA-HYDROXY-5-ANDROSTEN-17-ONE'>AND</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> | + | <table><tr><td colspan='2'>[[1q22]] is a 1 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=1Q22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q22 FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | |GENE= SULT2B1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <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=AND:3-BETA-HYDROXY-5-ANDROSTEN-17-ONE'>AND</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q22 OCA], [https://pdbe.org/1q22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q22 RCSB], [https://www.ebi.ac.uk/pdbsum/1q22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q22 ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=[[1q1q|1Q1Q]], [[1q1z|1Q1Z]], [[1q20|1Q20]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q22 OCA], [http://www.ebi.ac.uk/pdbsum/1q22 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1q22 RCSB]</span>
| + | == Function == |
| - | }}
| + | [https://www.uniprot.org/uniprot/ST2B1_HUMAN ST2B1_HUMAN] Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs and xenobiotic compounds. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Sulfates hydroxysteroids like DHEA. Isoform 1 preferentially sulfonates cholesterol, and isoform 2 avidly sulfonates pregnenolone but not cholesterol.<ref>PMID:9799594</ref> <ref>PMID:12145317</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q2/1q22_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1q22 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The gene for human hydroxysteroid sulfotransferase (SULT2B1) encodes two peptides, SULT2B1a and SULT2B1b, that differ only at their amino termini. SULT2B1b has a predilection for cholesterol but is also capable of sulfonating pregnenolone, whereas SULT2B1a preferentially sulfonates pregnenolone and only minimally sulfonates cholesterol. We have determined the crystal structure of SULT2B1a and SULT2B1b bound to the substrate donor product 3'-phosphoadenosine 5'-phosphate at 2.9 and 2.4 A, respectively, as well as SULT2B1b in the presence of the acceptor substrate pregnenolone at 2.3 A. These structures reveal a different catalytic binding orientation for the substrate from a previously determined structure of hydroxysteroid sulfotransferase (SULT2A1) binding dehydroepiandrosterone. In addition, the amino-terminal helix comprising residues Asp19 to Lys26, which determines the specificity difference between the SULT2B1 isoforms, becomes ordered upon pregnenolone binding, covering the substrate binding pocket. |
| | | | |
| - | '''Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of DHEA and PAP'''
| + | Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms.,Lee KA, Fuda H, Lee YC, Negishi M, Strott CA, Pedersen LC J Biol Chem. 2003 Nov 7;278(45):44593-9. Epub 2003 Aug 14. PMID:12923182<ref>PMID:12923182</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 1q22" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | The gene for human hydroxysteroid sulfotransferase (SULT2B1) encodes two peptides, SULT2B1a and SULT2B1b, that differ only at their amino termini. SULT2B1b has a predilection for cholesterol but is also capable of sulfonating pregnenolone, whereas SULT2B1a preferentially sulfonates pregnenolone and only minimally sulfonates cholesterol. We have determined the crystal structure of SULT2B1a and SULT2B1b bound to the substrate donor product 3'-phosphoadenosine 5'-phosphate at 2.9 and 2.4 A, respectively, as well as SULT2B1b in the presence of the acceptor substrate pregnenolone at 2.3 A. These structures reveal a different catalytic binding orientation for the substrate from a previously determined structure of hydroxysteroid sulfotransferase (SULT2A1) binding dehydroepiandrosterone. In addition, the amino-terminal helix comprising residues Asp19 to Lys26, which determines the specificity difference between the SULT2B1 isoforms, becomes ordered upon pregnenolone binding, covering the substrate binding pocket.
| + | *[[Sulfotransferase 3D structures|Sulfotransferase 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | 1Q22 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q22 OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms., Lee KA, Fuda H, Lee YC, Negishi M, Strott CA, Pedersen LC, J Biol Chem. 2003 Nov 7;278(45):44593-9. Epub 2003 Aug 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12923182 12923182]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Fuda, H.]] | + | [[Category: Fuda H]] |
| - | [[Category: Lee, K A.]] | + | [[Category: Lee KA]] |
| - | [[Category: Lee, Y C.]] | + | [[Category: Lee YC]] |
| - | [[Category: Negishi, M.]] | + | [[Category: Negishi M]] |
| - | [[Category: Pedersen, L C.]] | + | [[Category: Pedersen LC]] |
| - | [[Category: Strott, C A.]] | + | [[Category: Strott CA]] |
| - | [[Category: dhea]]
| + | |
| - | [[Category: pap]]
| + | |
| - | [[Category: sulfotransferase]]
| + | |
| - | [[Category: sult2b1b]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:07:46 2008''
| + | |
| Structural highlights
Function
ST2B1_HUMAN Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs and xenobiotic compounds. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Sulfates hydroxysteroids like DHEA. Isoform 1 preferentially sulfonates cholesterol, and isoform 2 avidly sulfonates pregnenolone but not cholesterol.[1] [2]
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 gene for human hydroxysteroid sulfotransferase (SULT2B1) encodes two peptides, SULT2B1a and SULT2B1b, that differ only at their amino termini. SULT2B1b has a predilection for cholesterol but is also capable of sulfonating pregnenolone, whereas SULT2B1a preferentially sulfonates pregnenolone and only minimally sulfonates cholesterol. We have determined the crystal structure of SULT2B1a and SULT2B1b bound to the substrate donor product 3'-phosphoadenosine 5'-phosphate at 2.9 and 2.4 A, respectively, as well as SULT2B1b in the presence of the acceptor substrate pregnenolone at 2.3 A. These structures reveal a different catalytic binding orientation for the substrate from a previously determined structure of hydroxysteroid sulfotransferase (SULT2A1) binding dehydroepiandrosterone. In addition, the amino-terminal helix comprising residues Asp19 to Lys26, which determines the specificity difference between the SULT2B1 isoforms, becomes ordered upon pregnenolone binding, covering the substrate binding pocket.
Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms.,Lee KA, Fuda H, Lee YC, Negishi M, Strott CA, Pedersen LC J Biol Chem. 2003 Nov 7;278(45):44593-9. Epub 2003 Aug 14. PMID:12923182[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Her C, Wood TC, Eichler EE, Mohrenweiser HW, Ramagli LS, Siciliano MJ, Weinshilboum RM. Human hydroxysteroid sulfotransferase SULT2B1: two enzymes encoded by a single chromosome 19 gene. Genomics. 1998 Nov 1;53(3):284-95. PMID:9799594 doi:http://dx.doi.org/10.1006/geno.1998.5518
- ↑ Fuda H, Lee YC, Shimizu C, Javitt NB, Strott CA. Mutational analysis of human hydroxysteroid sulfotransferase SULT2B1 isoforms reveals that exon 1B of the SULT2B1 gene produces cholesterol sulfotransferase, whereas exon 1A yields pregnenolone sulfotransferase. J Biol Chem. 2002 Sep 27;277(39):36161-6. Epub 2002 Jul 26. PMID:12145317 doi:http://dx.doi.org/10.1074/jbc.M207165200
- ↑ Lee KA, Fuda H, Lee YC, Negishi M, Strott CA, Pedersen LC. Crystal structure of human cholesterol sulfotransferase (SULT2B1b) in the presence of pregnenolone and 3'-phosphoadenosine 5'-phosphate. Rationale for specificity differences between prototypical SULT2A1 and the SULT2BG1 isoforms. J Biol Chem. 2003 Nov 7;278(45):44593-9. Epub 2003 Aug 14. PMID:12923182 doi:http://dx.doi.org/10.1074/jbc.M308312200
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