| Lamprey, 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... |
