3D model of lamprey estrogen receptor with estradiol and 15[alpha]-hydroxy-estradiol

Michael Baker,Charlie Chandsawangbhuwana,David Chang

doi:10.1038/npre.2009.2768.1

Michael Baker, Charlie Chandsawangbhuwana + Show 1 more

Open Access

https://doi.org/10.1038/npre.2009.2768.1

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Abstract

AbstractLamprey, a basal vertebrate, contains orthologs of the estrogen receptor (ER), progesterone receptor and corticoid receptor. A perplexing property of lamprey is that 15[alpha]-hydroxy-steroids are active steroids. For example, 15[alpha]-hydroxy-estradiol [15[alpha]-OH-E2] is the estrogen, instead of estradiol (E2). To investigate how 15[alpha]-OH-E2 binds lamprey ER, we constructed a 3D model of the lamprey ER with E2 and 15[alpha]-OH-E2. Our 3D model shows that S[delta] on Met-409 can form a hydrogen bond with the 15[alpha]-hydroxyl on 15[alpha]-OH-E2. In human ER[alpha], the corresponding residue Ile-424 has a van der Waals contact with 15[alpha]-OH-E2. BLAST analysis of GenBank indicates that among vertebrate ERs, only lamprey ER contains a methionine at this position. Thus, the contact between S[delta] on Met-409 and 15[alpha]-OH-E2 is unique. Our 3D model of lamprey ER should prove useful in virtual screening of chemical libraries to identify compounds for controlling reproduction in sea lamprey, an environmental pest in the Great Lakes in the USA.

Highlights

Lamprey and hagfish, two jawless fish, are at the base the vertebrate line, which has motivated studies of these fish to understand early events in vertebrate evolution
To determine if there is a structural basis in lamprey ER for the recognition of 15α-OHE2, we constructed a 3D model of lamprey ER complexed with E2 and 15α-OH-E2
This 3D model shows that Sδ on Met-409 in lamprey ER can have a hydrogen bond with 15α-hydroxyl on 15α-OH-E2

Summary

Introduction

Two jawless fish, are at the base the vertebrate line, which has motivated studies of these fish to understand early events in vertebrate evolution. This 3D model shows that Sδ on Met-409 in lamprey ER can have a hydrogen bond with 15α-hydroxyl on 15α-OH-E2. In human ERα, the corresponding residue is Ile-424, which has a van der Waals contact with 15α-OH-E2.

Results

Conclusion