Background: Lamprey, basal vertebrate, is an important model system for understanding early events in vertebrate evolution. Lamprey contains orthologs of the estrogen receptor [ER], progesterone receptor and corticoid receptor. A perplexing property of lamprey is that 15a-hydroxy-steroids are active steroids. For example, 15a-hydroxy-estradiol [15a-OH-E2] is the estrogen, instead of estradiol [E2]. To investigate how 15a-OH-E2 binds lamprey ER, we constructed a 3D model of the lamprey ER with E2 and 15a-OH-E2. Methodology: We used the 3D structure of human ERa as a template to construct a 3D model of lamprey ER. E2 and 15a-OH-E2 were inserted into the 3D model of lamprey ER and 15a-OH-E2 was inserted into human ERa. Then the each steroidprotein complex was refined using Discover 3 from Insight II software. To determine if lamprey ER had some regions that were unique among vertebrate ERs, we used the ligand-binding domain of lamprey ER as a query for a BLAST search of GenBank. Principal Findings: Our 3D model of lamprey ER with 15a-OH-E2 shows that Sd on Met-409 can form a hydrogen bond with the 15a-hydroxyl on 15a-OH-E2. In human ERa, the corresponding residue Ile-424 has a van der Waals contact with 15a-OH-E2. BLAST analysis of GenBank indicates that among vertebrate ERs, only lamprey ER contains a methionine at this position. Thus, the contact between Sd on Met-409 and 15a-OH-E2 is unique. Interestingly, BLAST finds that five New World monkey
To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.