4jkl: Difference between revisions
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<StructureSection load='4jkl' size='340' side='right'caption='[[4jkl]], [[Resolution|resolution]] 2.29Å' scene=''> | <StructureSection load='4jkl' size='340' side='right'caption='[[4jkl]], [[Resolution|resolution]] 2.29Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4jkl]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4jkl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_agalactiae_2603V/R Streptococcus agalactiae 2603V/R]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JKL FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4jkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jkl OCA], [https://pdbe.org/4jkl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jkl RCSB], [https://www.ebi.ac.uk/pdbsum/4jkl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jkl ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8E0N2_STRA5 Q8E0N2_STRA5] | |||
<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== | ||
*[[ | *[[Glucuronisidase 3D structures|Glucuronisidase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Streptococcus agalactiae 2603V/R]] | ||
[[Category: Redinbo | [[Category: Redinbo MR]] | ||
[[Category: Wallace | [[Category: Wallace BD]] | ||
Revision as of 14:18, 24 November 2022
Crystal Structure of Streptococcus agalactiae beta-glucuronidase in space group P21212Crystal Structure of Streptococcus agalactiae beta-glucuronidase in space group P21212
Structural highlights
FunctionPublication Abstract from PubMedThe selective inhibition of bacterial beta-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative beta-glucuronidases from the Firmicutes Streptococcus agalactiae and Clostridium perfringens and the Proteobacterium Escherichia coli, and the characterization of a beta-glucuronidase from the Bacteroidetes Bacteroides fragilis. While largely similar in structure, these enzymes exhibit marked differences in catalytic properties and propensities for inhibition, indicating that the microbiome maintains functional diversity in orthologous enzymes. Small changes in the structure of designed inhibitors can induce significant conformational changes in the beta-glucuronidase active site. Finally, we establish that beta-glucuronidase inhibition does not alter the serum pharmacokinetics of irinotecan or its metabolites in mice. Together, the data presented advance our in vitro and in vivo understanding of the microbial beta-glucuronidases, a promising new set of targets for controlling drug-induced gastrointestinal toxicity. Structure and Inhibition of Microbiome beta-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity.,Wallace BD, Roberts AB, Pollet RM, Ingle JD, Biernat KA, Pellock SJ, Venkatesh MK, Guthrie L, O'Neal SK, Robinson SJ, Dollinger M, Figueroa E, McShane SR, Cohen RD, Jin J, Frye SV, Zamboni WC, Pepe-Ranney C, Mani S, Kelly L, Redinbo MR Chem Biol. 2015 Sep 17;22(9):1238-49. doi: 10.1016/j.chembiol.2015.08.005. Epub, 2015 Sep 10. PMID:26364932[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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