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| | <StructureSection load='2o6l' size='340' side='right'caption='[[2o6l]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='2o6l' size='340' side='right'caption='[[2o6l]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2o6l]] 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=2O6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O6L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2o6l]] is a 2 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=2O6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O6L FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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]] 1.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UGT2B7 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glucuronosyltransferase Glucuronosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.17 2.4.1.17] </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=2o6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o6l OCA], [https://pdbe.org/2o6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o6l RCSB], [https://www.ebi.ac.uk/pdbsum/2o6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o6l 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=2o6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o6l OCA], [https://pdbe.org/2o6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o6l RCSB], [https://www.ebi.ac.uk/pdbsum/2o6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o6l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/UD2B7_HUMAN UD2B7_HUMAN]] UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.<ref>PMID:17442341</ref> Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).<ref>PMID:17442341</ref>
| + | [https://www.uniprot.org/uniprot/UD2B7_HUMAN UD2B7_HUMAN] UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.<ref>PMID:17442341</ref> Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).<ref>PMID:17442341</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glucuronosyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Miley, M J]] | + | [[Category: Miley MJ]] |
| - | [[Category: Redinbo, M R]] | + | [[Category: Redinbo MR]] |
| - | [[Category: Drug metabolism]]
| + | |
| - | [[Category: Enzyme]]
| + | |
| - | [[Category: Mad]]
| + | |
| - | [[Category: Nucleotide binding]]
| + | |
| - | [[Category: Rossman]]
| + | |
| - | [[Category: Sugar]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Udp-glucuronosyltransferase]]
| + | |
| - | [[Category: Ugt]]
| + | |
| Structural highlights
Function
UD2B7_HUMAN UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.[1] Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol (in vitro).[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
Human UDP-glucuronosyltransferases (UGT) are the dominant phase II conjugative drug metabolism enzymes that also play a central role in processing a range of endobiotic compounds. UGTs catalyze the covalent addition of glucuronic acid sugar moieties to a host of therapeutics and environmental toxins, as well as to a variety of endogenous steroids and other signaling molecules. We report the 1.8-A resolution apo crystal structure of the UDP-glucuronic acid binding domain of human UGT isoform 2B7 (UGT2B7), which catalyzes the conjugative elimination of opioid, antiviral, and anticancer drugs. This is the first crystal structure of any region of a mammalian UGT drug metabolism enzyme. Designated UGT2B7 mutants at residues predicted to interact with the UDP-glucuronic acid cofactor exhibited significantly impaired catalytic activity, with maximum effects observed for amino acids closest to the glucuronic acid sugar transferred to the acceptor molecule. Homology modeling of UGT2B7 with related plant flavonoid glucosyltransferases indicates human UGTs share a common catalytic mechanism. Point mutations at predicted catalytic residues in UGT2B7 abrogated activity, strongly suggesting human UGTs also utilize a serine hydrolase-like catalytic mechanism to facilitate glucuronic acid transfer.
Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7.,Miley MJ, Zielinska AK, Keenan JE, Bratton SM, Radominska-Pandya A, Redinbo MR J Mol Biol. 2007 Jun 1;369(2):498-511. Epub 2007 Mar 30. PMID:17442341[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Miley MJ, Zielinska AK, Keenan JE, Bratton SM, Radominska-Pandya A, Redinbo MR. Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7. J Mol Biol. 2007 Jun 1;369(2):498-511. Epub 2007 Mar 30. PMID:17442341 doi:10.1016/j.jmb.2007.03.066
- ↑ Miley MJ, Zielinska AK, Keenan JE, Bratton SM, Radominska-Pandya A, Redinbo MR. Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7. J Mol Biol. 2007 Jun 1;369(2):498-511. Epub 2007 Mar 30. PMID:17442341 doi:10.1016/j.jmb.2007.03.066
- ↑ Miley MJ, Zielinska AK, Keenan JE, Bratton SM, Radominska-Pandya A, Redinbo MR. Crystal structure of the cofactor-binding domain of the human phase II drug-metabolism enzyme UDP-glucuronosyltransferase 2B7. J Mol Biol. 2007 Jun 1;369(2):498-511. Epub 2007 Mar 30. PMID:17442341 doi:10.1016/j.jmb.2007.03.066
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