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==Catalytic S88C mutant of gut microbial sulfatase from Bacteroides fragilis CAG:558== | ==Catalytic S88C mutant of gut microbial sulfatase from Bacteroides fragilis CAG:558== | ||
<StructureSection load='6uss' size='340' side='right'caption='[[6uss]]' scene=''> | <StructureSection load='6uss' size='340' side='right'caption='[[6uss]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6USS OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6uss]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_fragilis_cag:558 Bacteroides fragilis cag:558]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6USS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6USS FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=6uss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uss OCA], [https://pdbe.org/6uss PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uss RCSB], [https://www.ebi.ac.uk/pdbsum/6uss PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uss ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Phase II drug metabolism inactivates xenobiotics and endobiotics through the addition of either a glucuronic acid or sulfate moiety prior to excretion, often via the gastrointestinal tract. While the human gut microbial beta-glucuronidase enzymes that reactivate glucuronide conjugates in the intestines are becoming well characterized and even controlled by targeted inhibitors, the sulfatases encoded by the human gut microbiome have not been comprehensively examined. Gut microbial sulfatases are poised to reactivate xenobiotics and endobiotics, which are then capable of undergoing enterohepatic recirculation or exerting local effects on the gut epithelium. Here, using protein structure-guided methods, we identify 728 distinct microbiome-encoded sulfatase proteins from the 4.8 million unique proteins present in the Human Microbiome Project Stool Sample database and 1766 gut microbial sulfatases from the 9.9 million sequences in the Integrated Gene Catalogue. We purify a representative set of these sulfatases, elucidate crystal structures, and pinpoint unique structural motifs essential to endobiotic sulfate processing. Gut microbial sulfatases differentially process sulfated forms of the neurotransmitters serotonin and dopamine, and the hormones melatonin, estrone, dehydroepiandrosterone, and thyroxine in a manner dependent both on variabilities in active site architecture and on markedly distinct oligomeric states. Taken together, these data provide initial insights into the structural and functional diversity of gut microbial sulfatases, providing a path toward defining the roles these enzymes play in health and disease. | |||
Structural Insights into Endobiotic Reactivation by Human Gut Microbiome-Encoded Sulfatases.,Ervin SM, Simpson JB, Gibbs ME, Creekmore BC, Lim L, Walton WG, Gharaibeh RZ, Redinbo MR Biochemistry. 2020 Oct 13;59(40):3939-3950. doi: 10.1021/acs.biochem.0c00711., Epub 2020 Sep 29. PMID:32993284<ref>PMID:32993284</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6uss" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Sulfatase 3D structures|Sulfatase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bacteroides fragilis cag:558]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ervin | [[Category: Ervin, S M]] | ||
[[Category: Redinbo | [[Category: Redinbo, M R]] | ||
[[Category: Arylsulfatase]] | |||
[[Category: Hydrolase]] | |||
[[Category: Microbiome]] | |||
Revision as of 12:23, 26 May 2021
Catalytic S88C mutant of gut microbial sulfatase from Bacteroides fragilis CAG:558Catalytic S88C mutant of gut microbial sulfatase from Bacteroides fragilis CAG:558
Structural highlights
Publication Abstract from PubMedPhase II drug metabolism inactivates xenobiotics and endobiotics through the addition of either a glucuronic acid or sulfate moiety prior to excretion, often via the gastrointestinal tract. While the human gut microbial beta-glucuronidase enzymes that reactivate glucuronide conjugates in the intestines are becoming well characterized and even controlled by targeted inhibitors, the sulfatases encoded by the human gut microbiome have not been comprehensively examined. Gut microbial sulfatases are poised to reactivate xenobiotics and endobiotics, which are then capable of undergoing enterohepatic recirculation or exerting local effects on the gut epithelium. Here, using protein structure-guided methods, we identify 728 distinct microbiome-encoded sulfatase proteins from the 4.8 million unique proteins present in the Human Microbiome Project Stool Sample database and 1766 gut microbial sulfatases from the 9.9 million sequences in the Integrated Gene Catalogue. We purify a representative set of these sulfatases, elucidate crystal structures, and pinpoint unique structural motifs essential to endobiotic sulfate processing. Gut microbial sulfatases differentially process sulfated forms of the neurotransmitters serotonin and dopamine, and the hormones melatonin, estrone, dehydroepiandrosterone, and thyroxine in a manner dependent both on variabilities in active site architecture and on markedly distinct oligomeric states. Taken together, these data provide initial insights into the structural and functional diversity of gut microbial sulfatases, providing a path toward defining the roles these enzymes play in health and disease. Structural Insights into Endobiotic Reactivation by Human Gut Microbiome-Encoded Sulfatases.,Ervin SM, Simpson JB, Gibbs ME, Creekmore BC, Lim L, Walton WG, Gharaibeh RZ, Redinbo MR Biochemistry. 2020 Oct 13;59(40):3939-3950. doi: 10.1021/acs.biochem.0c00711., Epub 2020 Sep 29. PMID:32993284[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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