Figure 1.
Structures of estradiol and 15α-hydroxy-estradiol.
Estradiol is the biologically active estrogen in most vertebrates. 15α-hydroxy-estradiol is found in lamprey blood [11], [12] and may be the biologically active estrogen.
Figure 2.
Alignment of lamprey ER with human ERα and human ERβ.
α-helices and β-strands from the crystal structures of ERα and ERβ are shaded in each sequence and notated below the alignment. Residues in human ERα involved in binding of estradiol are shown in green. Glu-419, which stabilizes His-524 is shaded in brown. Crystal structure accessions are human ERα [PDB: 1G50], human ERβ [1QKM].
Figure 3.
Overlap of 3D model of lamprey ER with human ERα.
The 3D model of lamprey ER with estradiol was superimposed on human ERα. There is excellent overlap. The root mean square deviation between the Cα backbone of human ERα and lamprey ER is 1.4 Å.
Figure 4.
Interaction of E2 with human ERα and the 3D model lamprey ER.
A. Interaction between E2 and human ERα. B. Interaction between E2 and the 3D model of lamprey ER. Lamprey ER has stabilizing interactions with the A ring of E2 similar to those in human ERα. His-509 has rotated and does not have a hydrogen bond with the C17-hydroxyl on E2. Instead, Cδ2 has a van der Waals contact with the C17-hydroxyl on E2. Also, Cε and Sδ on Met-409 have stabilizing contacts with C15 on E2.
Figure 5.
Interaction of 15α-OH-E2 with human ERα and the 3D model lamprey ER.
A. In human ERα, Cγ2 on Ile-424 and Cε on Met-421 have van der Waals contacts with 15α-OH-E2. B. Lamprey ER has stabilizing interactions with the A ring of 15α-OH-E2 that are similar to those in human ERα. His-509 has rotated and does not form a hydrogen bond with the C17-hydroxyl on E2. Cδ2 on His-509 has a van der Waals contact with the C17-hydroxyl. Sδ on Met-406 and Met-409 stabilize 15α-OH-E2.