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| - | [[Image:1bhs.gif|left|200px]]<br /> | |
| - | <applet load="1bhs" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1bhs, resolution 2.20Å" /> | |
| - | '''HUMAN ESTROGENIC 17BETA-HYDROXYSTEROID DEHYDROGENASE'''<br /> | |
| | | | |
| - | ==Overview== | + | ==HUMAN ESTROGENIC 17BETA-HYDROXYSTEROID DEHYDROGENASE== |
| - | BACKGROUND: The principal human estrogen, 17 beta-estradiol, is a potent, stimulator of certain endocrine-dependent forms of breast cancer. Because, human estrogenic 17 beta-hydroxysteroid dehydrogenase (type I 17 beta-HSD), catalyzes the last step in the biosynthesis of 17 beta-estradiol from the, less potent estrogen, estrone, it is an attractive target for the design, of inhibitors of estrogen production and tumor growth. This human enzyme, shares less than 15% sequence identity with a bacterial 3 alpha,20, beta-HSD, for which the three-dimensional structure is known. The amino, acid sequence of 17 beta-HSD also differs from that of bacterial 3, alpha,20 beta-HSD by two insertions (of 11 and 14 residues) and 52, additional residues at the C terminus. RESULTS: The 2.20 A resolution, structure of type I 17 beta-HSD, the first mammalian steroidogenic enzyme, studied by X-ray crystallographic techniques, reveals a fold, characteristic of the short-chain dehydrogenases. The active site contains, a Tyr-X-X-X-Lys sequence (where X is any amino acid) and a serine residue, features that are conserved in short-chain steroid dehydrogenases. The, structure also contains three alpha-helices and a helix-turn-helix motif, not observed in short-chain dehydrogenase structures reported previously., No cofactor density could be located. CONCLUSIONS: The helices present in, 17 beta-HSD that were not in the two previous short-chain dehydrogenase, structures are located at one end of the substrate-binding cleft away from, the catalytic triad. These helices restrict access to the active site and, appear to influence substrate specificity. Modeling the position of, estradiol in the active site suggests that a histidine side chain may play, a critical role in substrate recognition. One or more of these helices may, also be involved in the reported association of the enzyme with membranes., A model for steroid and cofactor binding as well as for the estrone to, estradiol transition state is proposed. The structure of the active site, provides a rational basis for designing more specific inhibitors of this, breast cancer associated enzyme.
| + | <StructureSection load='1bhs' size='340' side='right'caption='[[1bhs]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1bhs]] is a 1 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=1BHS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BHS FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</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=1bhs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bhs OCA], [https://pdbe.org/1bhs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bhs RCSB], [https://www.ebi.ac.uk/pdbsum/1bhs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bhs ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DHB1_HUMAN DHB1_HUMAN] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH. |
| | + | == 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/bh/1bhs_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/main_output.php?pdb_ID=1bhs ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==About this Structure== | + | ==See Also== |
| - | 1BHS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Structure known Active Site: CAT. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1BHS OCA].
| + | *[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Reference==
| + | </StructureSection> |
| - | Structure of human estrogenic 17 beta-hydroxysteroid dehydrogenase at 2.20 A resolution., Ghosh D, Pletnev VZ, Zhu DW, Wawrzak Z, Duax WL, Pangborn W, Labrie F, Lin SX, Structure. 1995 May 15;3(5):503-13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7663947 7663947]
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| - | [[Category: Estradiol 17-beta-dehydrogenase]]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Ghosh, D.]] | + | [[Category: Ghosh D]] |
| - | [[Category: estrogen]]
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| - | [[Category: human placental 17beta-hsd]]
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| - | [[Category: human type i 17beta-hsd]]
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| - | [[Category: oxidoreductase]]
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| - | [[Category: short-chain dehydrogenase]]
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| - | [[Category: steroid dehydrogenase]]
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| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:54:41 2007''
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