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3D Model of Lamprey Estrogen Receptor with Estradiol and 15α-Hydroxy-Estradiol

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 15α-hydroxy-steroids are active...

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Autores principales: Baker, Michael E., Chang, David J., Chandsawangbhuwana, Charlie
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698217/
https://www.ncbi.nlm.nih.gov/pubmed/19557178
http://dx.doi.org/10.1371/journal.pone.0006038
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author Baker, Michael E.
Chang, David J.
Chandsawangbhuwana, Charlie
author_facet Baker, Michael E.
Chang, David J.
Chandsawangbhuwana, Charlie
author_sort Baker, Michael E.
collection PubMed
description 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 15α-hydroxy-steroids are active steroids. For example, 15α-hydroxy-estradiol [15α-OH-E2] is the estrogen, instead of estradiol [E2]. To investigate how 15α-OH-E2 binds lamprey ER, we constructed a 3D model of the lamprey ER with E2 and 15α-OH-E2. METHODOLOGY: We used the 3D structure of human ERα as a template to construct a 3D model of lamprey ER. E2 and 15α-OH-E2 were inserted into the 3D model of lamprey ER and 15α-OH-E2 was inserted into human ERα. Then the each steroid-protein 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 15α-OH-E2 shows that Sδ on Met-409 can form a hydrogen bond with the 15α-hydroxyl on 15α-OH-E2. In human ERα, the corresponding residue Ile-424 has a van der Waals contact with 15α-OH-E2. BLAST analysis of GenBank indicates that among vertebrate ERs, only lamprey ER contains a methionine at this position. Thus, the contact between Sδ on Met-409 and 15α-OH-E2 is unique. Interestingly, BLAST finds that five New World monkeys and a sturgeon contain a valine instead of isoleucine. SIGNIFICANCE: In addition to shedding light on the structure of the ER in a basal vertebrate, 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 Lake Michigan.
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spelling pubmed-26982172009-06-24 3D Model of Lamprey Estrogen Receptor with Estradiol and 15α-Hydroxy-Estradiol Baker, Michael E. Chang, David J. Chandsawangbhuwana, Charlie PLoS One Research Article 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 15α-hydroxy-steroids are active steroids. For example, 15α-hydroxy-estradiol [15α-OH-E2] is the estrogen, instead of estradiol [E2]. To investigate how 15α-OH-E2 binds lamprey ER, we constructed a 3D model of the lamprey ER with E2 and 15α-OH-E2. METHODOLOGY: We used the 3D structure of human ERα as a template to construct a 3D model of lamprey ER. E2 and 15α-OH-E2 were inserted into the 3D model of lamprey ER and 15α-OH-E2 was inserted into human ERα. Then the each steroid-protein 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 15α-OH-E2 shows that Sδ on Met-409 can form a hydrogen bond with the 15α-hydroxyl on 15α-OH-E2. In human ERα, the corresponding residue Ile-424 has a van der Waals contact with 15α-OH-E2. BLAST analysis of GenBank indicates that among vertebrate ERs, only lamprey ER contains a methionine at this position. Thus, the contact between Sδ on Met-409 and 15α-OH-E2 is unique. Interestingly, BLAST finds that five New World monkeys and a sturgeon contain a valine instead of isoleucine. SIGNIFICANCE: In addition to shedding light on the structure of the ER in a basal vertebrate, 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 Lake Michigan. Public Library of Science 2009-06-25 /pmc/articles/PMC2698217/ /pubmed/19557178 http://dx.doi.org/10.1371/journal.pone.0006038 Text en Baker et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Baker, Michael E.
Chang, David J.
Chandsawangbhuwana, Charlie
3D Model of Lamprey Estrogen Receptor with Estradiol and 15α-Hydroxy-Estradiol
title 3D Model of Lamprey Estrogen Receptor with Estradiol and 15α-Hydroxy-Estradiol
title_full 3D Model of Lamprey Estrogen Receptor with Estradiol and 15α-Hydroxy-Estradiol
title_fullStr 3D Model of Lamprey Estrogen Receptor with Estradiol and 15α-Hydroxy-Estradiol
title_full_unstemmed 3D Model of Lamprey Estrogen Receptor with Estradiol and 15α-Hydroxy-Estradiol
title_short 3D Model of Lamprey Estrogen Receptor with Estradiol and 15α-Hydroxy-Estradiol
title_sort 3d model of lamprey estrogen receptor with estradiol and 15α-hydroxy-estradiol
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698217/
https://www.ncbi.nlm.nih.gov/pubmed/19557178
http://dx.doi.org/10.1371/journal.pone.0006038
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