6pyb
From Proteopedia
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<StructureSection load='6pyb' size='340' side='right'caption='[[6pyb]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='6pyb' size='340' side='right'caption='[[6pyb]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6pyb]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PYB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pyb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PYB FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=P5G:4,4-[(3R,4R)-oxolane-3,4-diylbis(methylene)]bis(2-methoxyphenol)'>P5G</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=P5G:4,4-[(3R,4R)-oxolane-3,4-diylbis(methylene)]bis(2-methoxyphenol)'>P5G</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SHBG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<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=6pyb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pyb OCA], [http://pdbe.org/6pyb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pyb RCSB], [http://www.ebi.ac.uk/pdbsum/6pyb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pyb ProSAT]</span></td></tr> | <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=6pyb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pyb OCA], [http://pdbe.org/6pyb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pyb RCSB], [http://www.ebi.ac.uk/pdbsum/6pyb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pyb ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/SHBG_HUMAN SHBG_HUMAN]] Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration. | [[http://www.uniprot.org/uniprot/SHBG_HUMAN SHBG_HUMAN]] Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration. | ||
| + | <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. | ||
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| + | 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> | ||
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| + | From MEDLINE®/PubMed®, 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__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Das, S]] | [[Category: Das, S]] | ||
Revision as of 12:10, 1 January 2020
Sex Hormone-binding globulin mutant E176K in complex with DVT
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