Estrogen receptor

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Human estrogen receptor-ligand binding domain (grey) complex with transcription intermediate factor-2 peptide (pink) and estradiol (PDB code 1gwr)

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Crystal structure of estradiol derived metal chelate and estrogen receptor-ligand binding domain complex 2yat

1 Estrogen receptors
2 Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs ^[1]
3 Estrogen receptor α complexed with raloxifene and a corepressor peptide

Estrogen receptors

(ER) are activated by the hormone estrogen (EST). The activated ER binds DNA and regulates the activity of many genes. There are 2 forms of ER: α and β and ER dimers can be of αα, ββ and αβ. ER is composed of 5 domains: N terminal A/B domain can transactivate transcription without binding estrogen; C domain (DBD) binds to Estrogen response elements of DNA; D domain is a hinge region; E domain is ligand binding (LBD) as well as binding the coactivator and corepressor proteins and transactivates gene transcription.

Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs ^[1]

Selective estrogen receptor modulators, such as estradiol 17-derived metal complexes, have been synthesized as targeted probes for the diagnosis and treatment of breast cancer. Here, we report the detailed 3D structure of bound with a novel at 2.6Å resolution (PDB ID 2yat). The residues with EPTA-Eu. The hydrogen bonds are shown as white dashed lines. of this structure with the structure of native ligand 17β-estradiol (E2) in the complex of E2/ERα-LBD complex (1ere) reveals that the . The made by additional estrogen receptor residues (e.g. Glu419 of H7 and Glu339 of H3, this depends on subunit), may work together with the E2 17β hydroxyl-His524 hydrogen bond and tighten the neck of the LBP upon binding of the endogenous ligand E2. 4-Hydroxytamoxifen (OHT) is an other selective estrogen receptor modulator. of EPTA-Eu/ERα-LBD complex on OHT/ERα-LBD complex (3ert) shows that there is similar network of hydrogen bonds in both complexes, except for His524 which does not form hydrogen bond with OHT in the OHT/ERα-LBD complex. E2/ERα-LBD (1ere), OHT/ERα-LBD (3ert) and EPTA-Eu/ERα-LBD shows that they overlap well in the majority portions of the domain, but differ significantly in the region of the 'omega loop'. They display different synergistic reciprocating movements, depending on the specific nature of the ligand bound. The structure of estrogen receptor complexed with EPTA-Eu provides important information pertinent to the design of novel functional ER targeted probes for clinical applications.

Estrogen receptor α complexed with raloxifene and a corepressor peptide

of estrogen receptor α complexed with raloxifene and a corepressor peptide (morph was taken from Gallery of Morphs of the Yale Morph Server).

For more details see

Ivan Koutsopatriy estrogen receptor
C-di-GMP receptors with PilZ domain
For more details on ERβ see Student Project 10 for UMass Chemistry 423 Spring 2015
For more details on ER-Tamoxifen complex see Tamoxifen.

3D structures of estrogen receptor

Updated on 22-May-2018

Reference

↑ Li MJ, Greenblatt HM, Dym O, Albeck S, Pais A, Gunanathan C, Milstein D, Degani H, Sussman JL. Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of selective estrogen receptor modulators. J Med Chem. 2011 Apr 7. PMID:21473635 doi:10.1021/jm200192y

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Joel L. Sussman, Alexander Berchansky

Retrieved from "http://52.214.119.220/wiki/index.php/Estrogen_receptor"

Category: Topic Page

@@ Line 27: / Line 27: @@
 {{#tree:id=OrganizedByTopic|openlevels=0|
-*Estrogen receptor α ligand binding domain
+*Estrogen receptor α ligand binding domain residues 245-554
 **[[4n1y]] - ERα LBD – pacific oyster<br />
@@ Line 36: / Line 36: @@
 **[[1err]], [[3ert]], [[1sj0]], [[1yim]], [[1r5k]], [[1xp1]], [[1xp6]], [[1xp9]], [[1xpc]], [[1xqc]], [[1yin]], [[2ouz]], [[2iog]], [[2iok]], [[3dt3]], [[3os8]], [[3os9]], [[3osa]], [[5t92]], [[5t97]] - hERα LBD + ligand<br />
 **[[4xi3]] - hERα LBD + bazedoxifene<br />
-**[[2bj4]], [[2jf9]], [[2jfa]], [[1pcg]] - hERα LBD + peptide antagonist<br />
+**[[2bj4]], [[2jf9]], [[2jfa]], [[1pcg]], [[5gtr]], [[5gs4]] - hERα LBD + peptide antagonist<br />
 **[[2q6j]], [[2p15]], [[3erd]], [[1l2i]] - hERα LBD + GRIP peptide<br />
+**[[6cbz]] - hERα LBD (mutant) + GRIP peptide + estradiol<br />
 **[[4q13]] - hERα LBD (mutant) + glucocorticoid receptor-interacting protein peptide<br />
 **[[5krf]] - hERα LBD (mutant) + peptide + anti-hormone<br />
 **[[2yat]] - hERα LBD (mutant) + EST derivative<br />
-**[[5fqp]], [[5fqr]], [[5fqs]], [[5fqt]], [[5fqv]], [[5aau]], [[5aav]], [[5acc]], [[5ak2]], [[5di7]], [[5did]], [[5die]], [[5dig]], [[5dk9]], [[5dkb]], [[5dke]], [[5dkg]], [[5dks]], [[5dl4]], [[5dlr]], [[5dmc]], [[5dmf]], [[5dp0]] - hERα LBD (mutant) + antagonist<br />
+**[[5fqp]], [[5fqr]], [[5fqs]], [[5fqt]], [[5fqv]], [[5aau]], [[5aav]], [[5acc]], [[5ak2]], [[5di7]], [[5did]], [[5die]], [[5dig]], [[5dk9]], [[5dkb]], [[5dke]], [[5dkg]], [[5dks]], [[5dl4]], [[5dlr]], [[5dmc]], [[5dmf]], [[5dp0]], [[6chz]], [[6chw]], [[6c42]], [[6b0f]], [[5w9d]], [[5ufx]], [[5ufw]] - hERα LBD (mutant) + antagonist<br />
+**[[4q50]] - hERα LBD (mutant) + tamoxifen derivative<br />
 **[[3uuc]] - hERα LBD + bisphenol<br />
 **[[5t1z]] - hERα LBD + LXXLL motif (mutant) + ethoxy triphenylethylene<br />
 **[[1gwr]] - hERα LBD + TIF2 peptide + EST<br />
 **[[2ocf]] - hERα LBD (mutant) + fibronectin domain 10 + EST<br />
+**[[2yja]] - hERα LBD + NCAO2 peptide<br />
+**[[2b23]] - hERα LBD (mutant) + NCAO2 peptide<br />
 *''ERα LBD ternary complex with nuclear receptor coactivator 2 peptide (NCAO2)''
 **[[2yja]] - hERα LBD + NCAO2 peptide<br />
-**[[5hyr]], [[5dx3]], [[5dxb]], [[4pxm]] - hERα LBD (mutant) + NCAO2 peptide + estradiol<br />
+**[[5hyr]], [[5dx3]], [[5dxb]], [[4pxm]], [[3q95]] - hERα LBD (mutant) + NCAO2 peptide + estradiol<br />
 **[[5dxb]] - hERα LBD (mutant) + NCAO2 peptide + stilbestrol derivative<br />
 **[[4zn7]] - hERα LBD + NCAO2 peptide + benzylidene estrone<br />
 **[[5kri]], [[5krj]], [[5krk]], [[5krl]], [[5krm]], [[5kro]] - hERα LBD (mutant) + NCAO2 peptide + anti-hormone<br />
 **[[5egv]], [[ehj]], [[5ei1]], [[5eit]], [[5dxk]], [[5dxe]], [[5dxg]], [[5kro]] - hERα LBD (mutant) + NCAO2 peptide + anti-hormone<br />
-**[[5dxe]], [[5dxg]], [[5dxk]], [[5dxm]], [[5dxp]], [[5dxq]], [[5dxr]], [[5dy8]], [[5dyb]], [[5dyd]], [[5dz0]], [[5dz1]], [[5dz3]], [[5dzh]], [[5dzi]], [[5e0w]], [[5e0x]], [[5e14]], [[5e15]], [[5e19]], [[5e1c]], [[5drj]], [[5drm]], [[5dtv]], [[5du5]], [[5due]], [[5dug]], [[5duh]], [[5dvs]], [[5dvv]], [[5dwe]], [[5dwg]], [[5dwi]], [[5dwj]] - hERα LBD (mutant) + NCAO2 peptide + antagonist<br />
+**[[5dxe]], [[5dxg]], [[5dxk]], [[5dxm]], [[5dxp]], [[5dxq]], [[5dxr]], [[5dy8]], [[5dyb]], [[5dyd]], [[5dz0]], [[5dz1]], [[5dz3]], [[5dzh]], [[5dzi]], [[5e0w]], [[5e0x]], [[5e14]], [[5e15]], [[5e19]], [[5e1c]], [[5drj]], [[5drm]], [[5dtv]], [[5du5]], [[5due]], [[5dug]], [[5duh]], [[5dvs]], [[5dvv]], [[5dwe]], [[5dwg]], [[5dwi]], [[5dwj]], [[4iu7]], [[4iui]], [[4iv2]], [[4iv4]], [[4ivw]], [[4ivy]], [[4iw6]], [[4iw8]], [[4iwc]], [[4iwf]], [[5u2d]], [[5tld]], [[5tlf]], [[5tlg]], [[5tll]], [[5tlm]], [[5tlo]], [[5tlp]], [[5tlt]], [[5tlu]], [[5tlv]], [[5tlx]], [[5tly]], [[5tm1]], [[5tm2]], [[5tm3]], [[5tm4]], [[5tm5]], [[5tm6]], [[5tm7]], [[5tm8]], [[5tm9]], [[5tml]], [[5tmo]], [[5tmm]], [[5tmq]], [[5tmr]], [[5tms]], [[5tmt]], [[5tmu]], [[5tmv]], [[5tmw]], [[5tmz]], [[5tn1]], [[5tn3]], [[5tn4]], [[5tn5]], [[5tn6]], [[5tn7]], [[5tn8]], [[5ehj]] - hERα LBD (mutant) + NCAO2 peptide + antagonist<br />
-**[[5kcf]], [[5kct]], [[5kcu]], [[5kcw]], [[5kd9]], [[5kcc]], [[5kcd]], [[4zn9]], [[4znh]], [[4zns]], [[4znt]], [[4znu]], [[4znv]], [[4znw]] - hERα LBD (mutant) + NCAO2 peptide + OBHS derivative<br />
+**[[5kcf]], [[5kct]], [[5kcu]], [[5kcw]], [[5kd9]], [[5kcc]], [[5kcd]], [[5kce]], [[4zn9]], [[4znh]], [[4zns]], [[4znt]], [[4znu]], [[4znv]], [[4znw]] - hERα LBD (mutant) + NCAO2 peptide + OBHS derivative<br />
 **[[5kr9]] - hERα LBD (mutant) + NCAO2 peptide + coumestrol<br />
+**[[2g5o]] - hERα LBD + NCAO2 peptide + EST derivative<br />
+**[[2qgt]], [[5krh]], [[5krc]], [[5kra]] - hERα LBD (mutant) + NCAO2 peptide + EST derivative<br />
+**[[1gwq]], [[2fai]], [[2g44]], [[2qzo]] - hERα LBD + NCAO2 peptide + ligand<br />
+**[[3l03]], [[3hm1]], [[3hlv]], [[1zky]], [[2b1v]], [[2b1z]], [[2qa6]], [[2qab]], [[2qgw]], [[2qh6]], [[2qr9]], [[2qse]], [[2qxm]] - hERα LBD (mutant) + NCAO2 peptide + ligand<br />
+**[[2qa8]] - hERα LBD (mutant) + NCAO2 peptide + genistein<br />
+**[[4pp6]], [[4ppp]], [[4pps]] - hERα LBD (mutant) + NCAO2 peptide  + resveratrol derivative<br />
 *''ERα LBD ternary complex with steroid receptor coactivator 1 peptide''
-**[[3uu7]], [[3uua]], [[3uud]] - hERα LBD (mutant) + nuclear receptor coactivator 1 peptide<br />
+**[[3uu7]], [[3uua]], [[3uud]] - hERα LBD (mutant) + NCAO1 peptide<br />
-**[[4dma]] - hERα LBD (mutant) + nuclear receptor coactivator 1 peptide + inhibitor<br />
+**[[4dma]] - hERα LBD (mutant) + NCAO1 peptide + inhibitor<br />
-**[[4mg5]], [[4mg6]], [[4mg7]], [[4mg8]], [[4mg9]], [[4mga]], [[4mgb]], [[4mgc]], [[4mgd]] - hERα LBD (mutant) + nuclear receptor coactivator 1 peptide + ligand<br />
+**[[4mg5]], [[4mg6]], [[4mg7]], [[4mg8]], [[4mg9]], [[4mga]], [[4mgb]], [[4mgc]], [[4mgd]] - hERα LBD (mutant) + NCAO1 peptide + ligand<br />
-**[[4tuz]] - hERα LBD (mutant) + steroid receptor coactivator 1 peptide + toxin<br />
+**[[4tuz]] - hERα LBD (mutant) + NCAO1 peptide + toxin<br />
-**[[4tv1]] - hERα LBD (mutant) + steroid receptor coactivator 1 peptide + preservative<br />
+**[[4tv1]] - hERα LBD (mutant) + NCAO1 peptide + preservative<br />
+**[[5jmm]] - hERα LBD (mutant) + NCAO1 peptide + biochanin<br />
 *''ERα LBD ternary complex with steroid receptor coactivator 2 peptide''
-**[[2b23]] - hERα LBD (mutant) + nuclear receptor coactivator 2 peptide<br />
+**[[2b23]] - hERα LBD (mutant) + NCAO2 peptide<br />
-**[[3q95]] - hERα LBD (mutant) + nuclear receptor coactivator 2 peptide + EST<br />
+**[[3q95]] - hERα LBD (mutant) + NCAO2 peptide + EST<br />
-**[[4iu7]], [[4iui]], [[4iv2]], [[4iv4]], [[4ivw]], [[4ivy]], [[4iw6]], [[4iw8]], [[4iwc]], [[4iwf]], [[5u2d]], [[5tld]], [[5tlf]], [[5tlg]], [[5tll]], [[5tlm]], [[5tlo]], [[5tlp]], [[5tlt]], [[5tlu]], [[5tlv]], [[5tlx]], [[5tly]], [[5tm1]], [[5tm2]], [[5tm3]], [[5tm4]], [[5tm5]], [[5tm6]], [[5tm7]], [[5tm8]], [[5tm9]], [[5tml]], [[5tmo]], [[5tmm]], [[5tmq]], [[5tmr]], [[5tms]], [[5tmt]], [[5tmu]], [[5tmv]], [[5tmw]], [[5tmz]], [[5tn1]], [[5tn3]], [[5tn4]], [[5tn5]], [[5tn6]], [[5tn7]], [[5tn8]] - hERα LBD (mutant) + nuclear receptor coactivator 2 peptide + inhibitor<br />
+**[[4iu7]], [[4iui]], [[4iv2]], [[4iv4]], [[4ivw]], [[4ivy]], [[4iw6]], [[4iw8]], [[4iwc]], [[4iwf]], [[5u2d]], [[5tld]], [[5tlf]], [[5tlg]], [[5tll]], [[5tlm]], [[5tlo]], [[5tlp]], [[5tlt]], [[5tlu]], [[5tlv]], [[5tlx]], [[5tly]], [[5tm1]], [[5tm2]], [[5tm3]], [[5tm4]], [[5tm5]], [[5tm6]], [[5tm7]], [[5tm8]], [[5tm9]], [[5tml]], [[5tmo]], [[5tmm]], [[5tmq]], [[5tmr]], [[5tms]], [[5tmt]], [[5tmu]], [[5tmv]], [[5tmw]], [[5tmz]], [[5tn1]], [[5tn3]], [[5tn4]], [[5tn5]], [[5tn6]], [[5tn7]], [[5tn8]] - hERα LBD (mutant) + NCAO2 peptide + inhibitor<br />
-**[[2g5o]] - hERα LBD + nuclear receptor coactivator 2 peptide + EST derivative<br />
+**[[2g5o]] - hERα LBD + NCAO2 peptide + EST derivative<br />
-**[[2qgt]] - hERα LBD (mutant) + nuclear receptor coactivator 2 peptide + EST derivative<br />
+**[[2qgt]] - hERα LBD (mutant) + NCAO2 peptide + EST derivative<br />
-**[[5kce]] - hERα LBD (mutant) + nuclear receptor coactivator 2 peptide + OBHS derivative<br />
+**[[5kce]] - hERα LBD (mutant) + NCAO2 peptide + OBHS derivative<br />
-**[[1gwq]], [[2fai]], [[2g44]], [[2qzo]] - hERα LBD + nuclear receptor coactivator 2 peptide + ligand<br />
+**[[1gwq]], [[2fai]], [[2g44]], [[2qzo]] - hERα LBD + NCAO2 peptide + ligand<br />
-**[[3l03]], [[3hm1]], [[3hlv]], [[1zky]], [[2b1v]], [[2b1z]], [[2qa6]], [[2qab]], [[2qgw]], [[2qh6]], [[2qr9]], [[2qse]], [[2qxm]] - hERα LBD (mutant) + nuclear receptor coactivator 2 peptide + ligand<br />
+**[[3l03]], [[3hm1]], [[3hlv]], [[1zky]], [[2b1v]], [[2b1z]], [[2qa6]], [[2qab]], [[2qgw]], [[2qh6]], [[2qr9]], [[2qse]], [[2qxm]] - hERα LBD (mutant) + NCAO2 peptide + ligand<br />
-**[[2qa8]] - hERα LBD (mutant) + steroid receptor coactivator 2 peptide + genistein<br />
+**[[2qa8]] - hERα LBD (mutant) + NCAO2 peptide + genistein<br />
-**[[4pp6]], [[4ppp]], [[4pps]] - hERα LBD (mutant) + steroid receptor coactivator peptide 2 + resveratrol derivative<br />
+**[[4pp6]], [[4ppp]], [[4pps]] - hERα LBD (mutant) + NCAO2 + resveratrol derivative<br />
 *''ERα LBD ternary complex with steroid receptor coactivator 3 peptide''
-**[[1x7r]] - hERα LBD + steroid receptor coactivator 3 peptide + genistein<br />
+**[[1x7r]] - hERα LBD + NCAO3 peptide + genistein<br />
-**[[1x7e]] - hERα LBD + nuclear receptor coactivator 3 peptide + ligand<br />
+**[[1x7e]] - hERα LBD + NCAO3 peptide + ligand<br />
 *Estrogen receptor β ligand binding domain
@@ Line 89: / Line 100: @@
 **[[1qkm]] - hERβ LBD + genistein<br />
 **[[1qkn]], [[1hj1]] - ERβ LBD + ligand – rat<br />
-**[[1nde]], [[1u3q]], [[1u3r]], [[1u3s]], [[2giu]], [[2i0g]], [[2i0j]], [[2jj3]], [[2z4b]], [[2qtu]] - hERβ LBD + ligand<br />
+**[[1nde]], [[1u3q]], [[1u3r]], [[1u3s]], [[2giu]], [[2i0g]], [[2i0j]], [[2jj3]], [[2z4b]], [[2qtu]], [[5toa]] - hERβ LBD + ligand<br />
 **[[2yly]] - hERβ LBD + sulfonamide agonist<br />
 **[[2fsz]] - hERβ LBD (mutant) + ligand<br />
@@ Line 98: / Line 109: @@
 *''ERβ LBD ternary complex with steroid receptor coactivator peptide''
-**[[1l2j]] - hERβ LBD + steroid receptor coactivator peptide + nonsteroidal EST<BR />
+**[[1l2j]] - hERβ LBD + NCAO peptide + nonsteroidal EST<BR />
-**[[2j7x]], [[3oll]], [[3ols]] - hERβ LBD + steroid receptor coactivator peptide + EST<BR />
+**[[2j7x]], [[3oll]], [[3ols]] - hERβ LBD + NCAO peptide + EST<BR />
-**[[1u9e]] - hERβ LBD + steroid receptor coactivator peptide<br />
+**[[1u9e]] - hERβ LBD + NCAO peptide<br />
-**[[1x76]], [[1x78]], [[1x7b]], [[1yy4]], [[1yye]], [[1zaf]], [[2j7y]], [[2nv7]], [[3omo]], [[3omp]], [[3omq]] - hERβ LBD + steroid receptor coactivator peptide + ligand<br />
+**[[1x76]], [[1x78]], [[1x7b]], [[1yy4]], [[1yye]], [[1zaf]], [[2j7y]], [[2nv7]], [[3omo]], [[3omp]], [[3omq]] - hERβ LBD + NCAO peptide + ligand<br />
-**[[1x7j]] - hERβ LBD + steroid receptor coactivator peptide + genistein
+**[[1x7j]] - hERβ LBD + NCAO peptide + genistein
-*Estrogen receptor α DNA binding domain
+*Estrogen receptor α DNA binding domain residues 182-252
 **[[1hcp]] – hERα DBD – NMR<br />

Estrogen receptor

From Proteopedia

Revision as of 07:17, 22 May 2018

Contents

Estrogen receptors

Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs ^[1]

Estrogen receptor α complexed with raloxifene and a corepressor peptide

For more details see

3D structures of estrogen receptor

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

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Estrogen receptor

From Proteopedia

Revision as of 07:17, 22 May 2018

Contents

Estrogen receptors

Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs [1]

Estrogen receptor α complexed with raloxifene and a corepressor peptide

For more details see

3D structures of estrogen receptor

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox

Structure of estradiol metal chelate and estrogen receptor complex: The basis for designing a new class of SERMs ^[1]