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| | ==Crystal structure of Ancestral variant b9 of SULT 1A1 in complex with PAP and 3-CyC== | | ==Crystal structure of Ancestral variant b9 of SULT 1A1 in complex with PAP and 3-CyC== |
| - | <StructureSection load='3qvv' size='340' side='right' caption='[[3qvv]], [[Resolution|resolution]] 2.35Å' scene=''> | + | <StructureSection load='3qvv' size='340' side='right'caption='[[3qvv]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qvv]] 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=3QVV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QVV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qvv]] 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=3QVV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QVV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3QV:7-HYDROXY-2-OXO-2H-CHROMENE-3-CARBONITRILE'>3QV</scene>, <scene name='pdbligand=A3P:ADENOSINE-3-5-DIPHOSPHATE'>A3P</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3QV:7-HYDROXY-2-OXO-2H-CHROMENE-3-CARBONITRILE'>3QV</scene>, <scene name='pdbligand=A3P:ADENOSINE-3-5-DIPHOSPHATE'>A3P</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qvu|3qvu]], [[1ls6|1ls6]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qvu|3qvu]], [[1ls6|1ls6]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SULT1A1, STP, STP1, OK/SW-cl.88 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SULT1A1, STP, STP1, OK/SW-cl.88 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aryl_sulfotransferase Aryl sulfotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.2.1 2.8.2.1] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Aryl_sulfotransferase Aryl sulfotransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.2.1 2.8.2.1] </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=3qvv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qvv OCA], [http://pdbe.org/3qvv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qvv RCSB], [http://www.ebi.ac.uk/pdbsum/3qvv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qvv 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=3qvv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qvv OCA], [https://pdbe.org/3qvv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qvv RCSB], [https://www.ebi.ac.uk/pdbsum/3qvv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qvv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ST1A1_HUMAN ST1A1_HUMAN]] Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. Has also estrogen sulfotransferase activity. responsible for the sulfonation and activation of minoxidil. Is Mediates the metabolic activation of carcinogenic N-hydroxyarylamines to DNA binding products and could so participate as modulating factor of cancer risk.<ref>PMID:12471039</ref> <ref>PMID:16221673</ref> | + | [[https://www.uniprot.org/uniprot/ST1A1_HUMAN ST1A1_HUMAN]] Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. Has also estrogen sulfotransferase activity. responsible for the sulfonation and activation of minoxidil. Is Mediates the metabolic activation of carcinogenic N-hydroxyarylamines to DNA binding products and could so participate as modulating factor of cancer risk.<ref>PMID:12471039</ref> <ref>PMID:16221673</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Sulfotransferase|Sulfotransferase]] | + | *[[Sulfotransferase 3D structures|Sulfotransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Aryl sulfotransferase]] | | [[Category: Aryl sulfotransferase]] |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Alkolombri, U]] | | [[Category: Alkolombri, U]] |
| | [[Category: Elias, M]] | | [[Category: Elias, M]] |
| | [[Category: Tawfik, D S]] | | [[Category: Tawfik, D S]] |
| | [[Category: Transferase]] | | [[Category: Transferase]] |
| Structural highlights
3qvv is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | |
| Gene: | SULT1A1, STP, STP1, OK/SW-cl.88 (HUMAN) |
| Activity: | Aryl sulfotransferase, with EC number 2.8.2.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ST1A1_HUMAN] Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters. Has also estrogen sulfotransferase activity. responsible for the sulfonation and activation of minoxidil. Is Mediates the metabolic activation of carcinogenic N-hydroxyarylamines to DNA binding products and could so participate as modulating factor of cancer risk.[1] [2]
Publication Abstract from PubMed
Large libraries of randomly mutated genes are applied in directed evolution experiments in order to obtain sufficient variability. These libraries, however, contain mostly inactive variants, and the very low frequency of improved variants can only be isolated by high-throughput screening. Small but efficient libraries comprise an attractive alternative. Here, we describe the application of ancestral libraries-libraries based on mutations predicted by phylogenetic analysis and ancestral inference. We designed and constructed such libraries using serum paraoxonases and cytosolic sulfotransferases (SULTs) as model enzymes. Both of these enzyme families exhibit a range of activities in drug metabolism and detoxification of xenobiotics. The ancestral serum paraoxonase and SULT libraries were screened by low-throughput means, including HPLC, using substrates and/or reactions with which all family members exhibit low activity. The libraries showed a remarkably high frequency of highly polymorphic and functionally diverse variants. Screening of as few as 300 variants enabled the isolation of mutants with up to 50-fold higher activity than the starting point enzyme. Structural and kinetic characterizations of an evolved SULT variant show how few ancestral mutations reshaped the active site and modulated the enzyme's specificity. Ancestral libraries therefore comprise a means of focusing diversity to positions and mutations that readily trigger changes in substrate and/or reaction specificity, thereby facilitating the isolation of new enzyme variants for a variety of different substrates and reactions by medium-throughput or even low-throughput screens.
Directed evolution of sulfotransferases and paraoxonases by ancestral libraries.,Alcolombri U, Elias M, Tawfik DS J Mol Biol. 2011 Aug 26;411(4):837-53. Epub 2011 Jun 24. PMID:21723874[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gamage NU, Duggleby RG, Barnett AC, Tresillian M, Latham CF, Liyou NE, McManus ME, Martin JL. Structure of a human carcinogen-converting enzyme, SULT1A1. Structural and kinetic implications of substrate inhibition. J Biol Chem. 2003 Feb 28;278(9):7655-62. Epub 2002 Dec 5. PMID:12471039 doi:http://dx.doi.org/10.1074/jbc.M207246200
- ↑ Gamage NU, Tsvetanov S, Duggleby RG, McManus ME, Martin JL. The structure of human SULT1A1 crystallized with estradiol. An insight into active site plasticity and substrate inhibition with multi-ring substrates. J Biol Chem. 2005 Dec 16;280(50):41482-6. Epub 2005 Oct 12. PMID:16221673 doi:10.1074/jbc.M508289200
- ↑ Alcolombri U, Elias M, Tawfik DS. Directed evolution of sulfotransferases and paraoxonases by ancestral libraries. J Mol Biol. 2011 Aug 26;411(4):837-53. Epub 2011 Jun 24. PMID:21723874 doi:10.1016/j.jmb.2011.06.037
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