View source for 6pyb


==Sex Hormone-binding globulin mutant E176K in complex with DVT==
<StructureSection load='6pyb' size='340' side='right'caption='[[6pyb]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6pyb]] 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=6PYB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PYB 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=P5G:2-methoxy-4-[[(3~{R},4~{R})-4-[(3-methoxy-4-oxidanyl-phenyl)methyl]oxolan-3-yl]methyl]phenol'>P5G</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=6pyb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pyb OCA], [https://pdbe.org/6pyb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pyb RCSB], [https://www.ebi.ac.uk/pdbsum/6pyb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pyb ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sex hormone-binding globulin (SHBG) determines the equilibrium between free and protein-bound androgens and estrogens in the blood and regulates their access to target tissues. Using crystallographic approaches and radiolabeled competitive binding-capacity assays, we report here how two non-steroidal compounds bind to human SHBG, and how they influence androgen activity in cell culture. We found that one of these compounds, (-)3,4-divanillyltetrahydrofuran (DVT), present in stinging nettle root extracts and used as a nutraceutical, binds SHBG with relatively low affinity. By contrast a, synthetic compound, 3-(1H-imidazol-1-ylmethyl)-2phenyl-1H-indole (IPI), bound SHBG with an affinity similar to that of testosterone and estradiol. Crystal structures of SHBG in complex with DVT or IPI at 1.71-1.80 A resolutions revealed their unique orientations in the SHBG ligand-binding pocket and suggested opportunities for the design of other non-steroidal ligands of SHBG. As observed for estradiol but not testosterone, IPI binding to SHBG was reduced by ~20 fold in the presence of zinc, whereas DVT binding was almost completely lost. Estradiol dependent fibulin-2 interactions with SHBG similarly occurred for IPI-bound SHBG, but not with DVT-bound SHBG. Both DVT and IPI increased the activity of testosterone in a cell culture androgen reporter system by competitively displacing testosterone from SHBG. These findings indicate how non-steroidal ligands of SHBG maybe designed to modulate the bioavailability of sex steroids.

Molecular interactions between sex hormone-binding globulin and non-steroidal ligands that enhance androgen action.,Round P, Das S, Wu TS, Wahala K, Van Petegem F, Hammond GL J Biol Chem. 2019 Dec 18. pii: RA119.011051. doi: 10.1074/jbc.RA119.011051. PMID:31852737<ref>PMID:31852737</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6pyb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Das S]]
[[Category: Round PW]]
[[Category: Van Petegem F]]