Interaction of E2 with amino acids in human ERα and ERβ. A.

<p>Interaction of E2 with human ERα <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Eiler1" target="_blank">[24]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Brzozowski1" target="_blank">[33]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Warnmark1" target="_blank">[34]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Tanenbaum1" target="_blank">[36]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Baker3" target="_blank">[37]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Baker4" target="_blank">[38]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Katzenellenbogen1" target="_blank">[39]</a>. The phenolic hydroxyl of E2 contacts Glu-353, Arg-394 and Leu-387. The 17β-hydroxyl contacts His524 and Leu-525. The D ring contacts Met343, Met421, Gly-521 and Ile-424. Favorable van der Waals contacts have a distance of 4.25 Å or less between E2 and amino acids on ERα. <b>B.</b> Interaction of E2 with human ERβ <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Mocklinghoff1" target="_blank">[28]</a>. The phenolic hydroxyl of E2 contacts Glu-305, Arg-346 and Leu-339. The 17β-hydroxyl contacts Gly-472, His473 and Leu-476. The D ring contacts Met-336 and Ile-373. Favorable van der Waals contacts have a distance of 4.25 Å or less between E2 and amino acids on ERβ.</p

Distances between E2 and ERα and ERβ.

<p>Distances between E2 and ERα and ERβ.</p

Distances between MBP and ERβ.

<p>Distances between MBP and ERβ.</p

Structures of bisphenols that are potent synthetic estrogens.

<p>Bisphenols, linked with one, two or three carbons, can have high affinity for ERs. 3-(3-fluoropropyl)cyclofenil, hexestrol and benzestrol have a higher affinity for ERα that does E2 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Kuiper1" target="_blank">[18]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Katzenellenbogen1" target="_blank">[39]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Seo1" target="_blank">[40]</a>.</p

Distances between BPA and ERβ.

<p>Distances between BPA and ERβ.</p

Analysis of two 3D models of BPA in human ERα. A.

<p>3D model of BPA in orientation 1 in human ERα. The first phenolic ring on BPA contacts Glu-353, Arg-394 and Phe-404 on ERα, but does not contact either Leu-387 or Leu-391. Moreover, the second phenolic ring does not contact either Gly-521, His-524 or Leu-525. Instead, the second phenolic ring contacts Phe-404, Met-421 and Ile-424. <b>B.</b> 3D model of BPA in orientation 2 in human ERα. The first phenolic ring on BPA contacts Glu-353 and Arg-394 on ERα, but does not contact Leu-387 or Phe-404. The second phenolic ring does not contact either Gly-521 or His-524. Instead, the second phenolic ring has novel contacts with Thr-347 and Leu-384.</p

Analysis of two 3D models of BPA in human ERβ. A.

<p>3D model of BPA in orientation 1 in human ERβ. The first phenolic ring on BPA contacts Glu-305, Arg-346, and Phe-356, but does not contact either the backbone oxygen on Leu-339 or Cδ2 on Leu-343. The second phenolic ring contacts Gly-472, His-475 and Leu-476. <b>B.</b> 3D model of BPA in orientation 2 in human ERβ. The first phenolic ring on BPA contacts Glu-305, Arg-346, Phe-356, the backbone oxygen on Leu-339 and Cδ2 on Leu-343. The second phenolic ring does not contact either Gly-472, His-475 or Leu-476.</p

Analysis of two 3D models of MBP in human ERα. A.

<p>3D model of MBP in orientation 1 in human ERα. The first phenolic ring on MBP contacts Glu-353, Arg-394 and Phe-404 on ERα and the second phenolic ring contacts Gly-521, His-524 and Leu-525. Favorable van der Waals contacts have a distance of 4.25 Å or less between MBP and amino acids on ERα. <b>B.</b> 3D model of MBP in orientation 2 in human ERα. The first phenolic ring on MBP contacts Glu-353, Arg-394 and Phe-404 on ERα, and the second phenolic ring contacts Gly-521, His-524 and Leu-525. However, in contrast to Orientation 1, the backbone oxygen on Leu-387 does not contact the phenolic hydroxyl on MBP. Phe-404 and Met-421 do not have van der Waals contacts with the linker between the two phenolic rings on MBP.</p

Docking analysis of MBP and BPA in ERα and ERβ.

<p>X-Score Analysis of MBP and BPA in ERα and ERβ <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Cheng1" target="_blank">[29]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046078#pone.0046078-Wang1" target="_blank">[30]</a>.</p

Distances between MBP and ERα.

<p>Distances between MBP and ERα.</p