6cgc: Difference between revisions

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'''Unreleased structure'''


The entry 6cgc is ON HOLD  until Paper Publication
==Crystal structure of human 17beta-HSD type 1 in ternary complex with 2-MeO-CC-156 and NADP+==
<StructureSection load='6cgc' size='340' side='right'caption='[[6cgc]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6cgc]] 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=6CGC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CGC 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6cgc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cgc OCA], [https://pdbe.org/6cgc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cgc RCSB], [https://www.ebi.ac.uk/pdbsum/6cgc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cgc 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


Authors: Li, T., Lin, S.X.
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>


Description: Crystal structure of human 17beta-HSD type 1 in ternary complex with MeO-CC-156 and NADP+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Lin, S.X]]
<div class="pdbe-citations 6cgc" style="background-color:#fffaf0;"></div>
[[Category: Li, T]]
 
==See Also==
*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li T]]
[[Category: Lin SX]]
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