1i5r: Difference between revisions

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-[[Image:1i5r.png|left|200px]]
+==TYPE 1 17-BETA HYDROXYSTEROID DEHYDROGENASE EM1745 COMPLEX==
+<StructureSection load='1i5r' size='340' side='right' caption='[[1i5r]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1i5r]] is a 1 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=1I5R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1I5R FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HYC:O5-[9-(3,17B-DIHYDROXY-1,3,5(10)-ESTRATRIEN-16B-YL)-NONANOYL]ADENOSINE'>HYC</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1iol|1iol]]</td></tr>
+<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Estradiol_17-beta-dehydrogenase Estradiol 17-beta-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </span></td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1i5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i5r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1i5r RCSB], [http://www.ebi.ac.uk/pdbsum/1i5r PDBsum]</span></td></tr>
+<table>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i5/1i5r_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD type 1) catalyzes the final step in the synthesis of active estrogens that stimulate the proliferation of breast cancer cells. Based on the initial premise to make use of the binding energies of both the substrate and cofactor sites, and molecular modeling starting from the enzyme structure, several estradiol-adenosine hybrids were designed and synthesized. Among these hybrids, EM-1745 with a linker of 8-CH2 groups is proved to be the best competitive inhibitor with a Ki of 3.0 +/- 0.8 nM. The crystal structure of the EM-1745 enzyme complex at 1.6 A provides evidence at atomic resolution of strong interactions between both the steroid and cofactor moieties and the enzyme molecule, as illustrated by a deltaA-weighted 2Fo-Fc electron density map contoured at 3.0 delta. The substrate entry loop is further stabilized in this complex compared with previous complexes of the enzyme. These results confirm our initial strategy of combining studies of structural biology and enzyme mechanism in the inhibitor design, which may be applied to other steroidogenic enzymes involved in human diseases.
-{{STRUCTURE_1i5r|  PDB=1i5r  |  SCENE=  }}
+A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity.,Qiu W, Campbell RL, Gangloff A, Dupuis P, Boivin RP, Tremblay MR, Poirier D, Lin SX FASEB J. 2002 Nov;16(13):1829-31. Epub 2002 Sep 5. PMID:12223444<ref>PMID:12223444</ref>
-===TYPE 1 17-BETA HYDROXYSTEROID DEHYDROGENASE EM1745 COMPLEX===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_12223444}}
-==About this Structure==
-[[1i5r]] is a 1 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=1I5R OCA].
 ==See Also==
 *[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:012223444</ref><ref group="xtra">PMID:018533708</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Estradiol 17-beta-dehydrogenase]]
 [[Category: Homo sapiens]]