6cgc

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'''Unreleased structure'''
 
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The entry 6cgc is ON HOLD until Paper Publication
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==Crystal structure of human 17beta-HSD type 1 in ternary complex with 2-MeO-CC-156 and NADP+==
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<StructureSection load='6cgc' size='340' side='right' caption='[[6cgc]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6cgc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CGC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CGC FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F0A:3-{[(9beta,14beta,16alpha,17alpha)-3,17-dihydroxy-2-methoxyestra-1,3,5(10)-trien-16-yl]methyl}benzamide'>F0A</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-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>
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<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=6cgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cgc OCA], [http://pdbe.org/6cgc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cgc RCSB], [http://www.ebi.ac.uk/pdbsum/6cgc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cgc ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/DHB1_HUMAN DHB1_HUMAN]] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) plays a pivotal role in the progression of estrogen-related diseases because of its involvement in the biosynthesis of estradiol (E2), constituting a valuable therapeutic target for endocrine treatment. In the present study, we successfully cocrystallized the enzyme with the reversible inhibitor 2-methoxy-16beta-( m-carbamoylbenzyl)-E2 (2-MeO-CC-156) as well as the enzyme with the irreversible inhibitor 3-(2-bromoethyl)-16beta-( m-carbamoylbenzyl)-17beta-hydroxy-1,3,5(10)-estratriene (PBRM). The structures of ternary complexes of 17beta-HSD1-2-MeO-CC-156-NADP(+) and 17beta-HSD1-PBRM-NADP(+) comparatively show the formation of a covalent bond between His(221) and the bromoethyl side chain of the inhibitor in the PBRM structure. A dynamic process including beneficial molecular interactions that favor the specific binding of a low-reactivity inhibitor and subsequent N-alkylation event through the participation of His(221) in the enzyme catalytic site clearly demonstrates the covalent bond formation. This finding opens the door to a new design of alkyl halide-based specific covalent inhibitors as potential therapeutic agents for different enzymes, contributing to the development of highly efficient inhibitors.
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Authors: Li, T., Lin, S.X.
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Combined Biophysical Chemistry Reveals a New Covalent Inhibitor with a Low-Reactivity Alkyl Halide.,Li T, Maltais R, Poirier D, Lin SX J Phys Chem Lett. 2018 Sep 20;9(18):5275-5280. doi: 10.1021/acs.jpclett.8b02225. , Epub 2018 Aug 31. PMID:30148957<ref>PMID:30148957</ref>
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Description: Crystal structure of human 17beta-HSD type 1 in ternary complex with MeO-CC-156 and NADP+
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Lin, S.X]]
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<div class="pdbe-citations 6cgc" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: 17-beta-estradiol 17-dehydrogenase]]
[[Category: Li, T]]
[[Category: Li, T]]
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[[Category: Lin, S X]]
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[[Category: Complex]]
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[[Category: Hydroxysteroid dehydrogenase]]
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[[Category: Inhibitor]]
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[[Category: Oxidoreductase]]

Revision as of 12:04, 16 January 2019

Crystal structure of human 17beta-HSD type 1 in ternary complex with 2-MeO-CC-156 and NADP+

6cgc, resolution 2.10Å

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