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| | <StructureSection load='6pyf' size='340' side='right'caption='[[6pyf]], [[Resolution|resolution]] 1.73Å' scene=''> | | <StructureSection load='6pyf' size='340' side='right'caption='[[6pyf]], [[Resolution|resolution]] 1.73Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6pyf]] 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=6PYF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PYF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pyf]] 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=6PYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PYF 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=EST:ESTRADIOL'>EST</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.73Å</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='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=EST:ESTRADIOL'>EST</scene></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=6pyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pyf OCA], [http://pdbe.org/6pyf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pyf RCSB], [http://www.ebi.ac.uk/pdbsum/6pyf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pyf ProSAT]</span></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=6pyf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pyf OCA], [https://pdbe.org/6pyf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pyf RCSB], [https://www.ebi.ac.uk/pdbsum/6pyf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pyf 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. | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Das, S]] | + | [[Category: Das S]] |
| - | [[Category: Petegem, F Van]] | + | [[Category: Round PW]] |
| - | [[Category: Round, P W]] | + | [[Category: Van Petegem F]] |
| - | [[Category: Wu, T S]] | + | [[Category: Wu TS]] |
| - | [[Category: Binding globulin]]
| + | |
| - | [[Category: Hormone]]
| + | |
| - | [[Category: Sex steroid]]
| + | |
| - | [[Category: Transport]]
| + | |
| Structural highlights
Function
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Round P, Das S, Wu TS, Wahala K, Van Petegem F, Hammond GL. Molecular interactions between sex hormone-binding globulin and non-steroidal ligands that enhance androgen action. J Biol Chem. 2019 Dec 18. pii: RA119.011051. doi: 10.1074/jbc.RA119.011051. PMID:31852737 doi:http://dx.doi.org/10.1074/jbc.RA119.011051
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