3uuc

From Proteopedia

(Difference between revisions)

Revision as of 09:12, 2 July 2014

Crystal structure of hERa-LBD (wt) in complex with bisphenol-C

Structural highlights

3uuc is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	3uu7, 3uua, 3uud
Gene:	ESR1, ESR, NR3A1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Publication Abstract from PubMed

Bisphenol A (BPA) is an industrial compound and a well known endocrine-disrupting chemical with estrogenic activity. The widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Here we report that the mechanisms by which BPA and two congeners, bisphenol AF and bisphenol C (BPC), bind to and activate estrogen receptors (ER) alpha and beta differ from that used by 17beta-estradiol. We show that bisphenols act as partial agonists of ERs by activating the N-terminal activation function 1 regardless of their effect on the C-terminal activation function 2, which ranges from weak agonism (with BPA) to antagonism (with BPC). Crystallographic analysis of the interaction between bisphenols and ERs reveals two discrete binding modes, reflecting the different activities of compounds on ERs. BPA and 17beta-estradiol bind to ERs in a similar fashion, whereas, with a phenol ring pointing toward the activation helix H12, the orientation of BPC accounts for the marked antagonist character of this compound. Based on structural data, we developed a protocol for in silico evaluation of the interaction between bisphenols and ERs or other members of the nuclear hormone receptor family, such as estrogen-related receptor gamma and androgen receptor, which are two known main targets of bisphenols. Overall, this study provides a wealth of tools and information that could be used for the development of BPA substitutes devoid of nuclear hormone receptor-mediated activity and more generally for environmental risk assessment.

Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes.,Delfosse V, Grimaldi M, Pons JL, Boulahtouf A, le Maire A, Cavailles V, Labesse G, Bourguet W, Balaguer P Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):14930-5. Epub 2012 Aug 27. PMID:22927406^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Delfosse V, Grimaldi M, Pons JL, Boulahtouf A, le Maire A, Cavailles V, Labesse G, Bourguet W, Balaguer P. Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes. Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):14930-5. Epub 2012 Aug 27. PMID:22927406 doi:http://dx.doi.org/10.1073/pnas.1203574109

1 Structural highlights
2 Publication Abstract from PubMed
3 See Also
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3uuc"

@@ Line 1: / Line 1: @@
-[[Image:3uuc.png|left|200px]]
+==Crystal structure of hERa-LBD (wt) in complex with bisphenol-C==
+<StructureSection load='3uuc' size='340' side='right' caption='[[3uuc]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3uuc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3UUC FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0D1:4,4-(2,2-DICHLOROETHENE-1,1-DIYL)DIPHENOL'>0D1</scene><br>
+<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3uu7|3uu7]], [[3uua|3uua]], [[3uud|3uud]]</td></tr>
+<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ESR1, ESR, NR3A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3uuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uuc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3uuc RCSB], [http://www.ebi.ac.uk/pdbsum/3uuc PDBsum]</span></td></tr>
+<table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Bisphenol A (BPA) is an industrial compound and a well known endocrine-disrupting chemical with estrogenic activity. The widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Here we report that the mechanisms by which BPA and two congeners, bisphenol AF and bisphenol C (BPC), bind to and activate estrogen receptors (ER) alpha and beta differ from that used by 17beta-estradiol. We show that bisphenols act as partial agonists of ERs by activating the N-terminal activation function 1 regardless of their effect on the C-terminal activation function 2, which ranges from weak agonism (with BPA) to antagonism (with BPC). Crystallographic analysis of the interaction between bisphenols and ERs reveals two discrete binding modes, reflecting the different activities of compounds on ERs. BPA and 17beta-estradiol bind to ERs in a similar fashion, whereas, with a phenol ring pointing toward the activation helix H12, the orientation of BPC accounts for the marked antagonist character of this compound. Based on structural data, we developed a protocol for in silico evaluation of the interaction between bisphenols and ERs or other members of the nuclear hormone receptor family, such as estrogen-related receptor gamma and androgen receptor, which are two known main targets of bisphenols. Overall, this study provides a wealth of tools and information that could be used for the development of BPA substitutes devoid of nuclear hormone receptor-mediated activity and more generally for environmental risk assessment.
-{{STRUCTURE_3uuc|  PDB=3uuc  |  SCENE=  }}
+Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes.,Delfosse V, Grimaldi M, Pons JL, Boulahtouf A, le Maire A, Cavailles V, Labesse G, Bourguet W, Balaguer P Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):14930-5. Epub 2012 Aug 27. PMID:22927406<ref>PMID:22927406</ref>
-===Crystal structure of hERa-LBD (wt) in complex with bisphenol-C===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_22927406}}
+==See Also==
+*[[Estrogen receptor|Estrogen receptor]]
-==About this Structure==
+== References ==
-[[3uuc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UUC OCA].
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
 [[Category: Bourguet, W.]]

3uuc

From Proteopedia

Revision as of 09:12, 2 July 2014

Crystal structure of hERa-LBD (wt) in complex with bisphenol-C

Structural highlights

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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