2o6l

From Proteopedia

(Difference between revisions)

Revision as of 06:41, 11 September 2015

Crystal Structure of the UDP-Glucuronic Acid Binding Domain of the Human Drug Metabolizing UDP-Glucuronosyltransferase 2B7

Structural highlights

2o6l 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.
NonStd Res:
Gene:	UGT2B7 (HUMAN)
Activity:	Glucuronosyltransferase, with EC number 2.4.1.17
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2o6l"

@@ Line 2: / Line 2: @@
 <StructureSection load='2o6l' size='340' side='right' caption='[[2o6l]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2o6l]] is a 2 chain structure with 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=2O6L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2O6L FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2o6l]] 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=2O6L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/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>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UGT2B7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UGT2B7 ([http://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/Glucuronosyltransferase Glucuronosyltransferase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o6l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2o6l RCSB], [http://www.ebi.ac.uk/pdbsum/2o6l PDBsum]</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=2o6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o6l OCA], [http://pdbe.org/2o6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2o6l RCSB], [http://www.ebi.ac.uk/pdbsum/2o6l PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 26: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2o6l" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 31: / Line 34: @@
 </StructureSection>
 [[Category: Glucuronosyltransferase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Miley, M J]]
 [[Category: Redinbo, M R]]

2o6l

From Proteopedia

Revision as of 06:41, 11 September 2015

Crystal Structure of the UDP-Glucuronic Acid Binding Domain of the Human Drug Metabolizing UDP-Glucuronosyltransferase 2B7

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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