Fine spatial assembly for construction of the phenol-binding pocket to capture bisphenol a in the human nuclear receptor estrogen-related receptor γ

Xiaohui Liu, Ayami Matsushima, Masayuki Nakamura, Tommaso Costa, Takeru Nose, Yasuyuki Shimohigashi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Various lines of evidence have shown that bisphenol A (BPA) acts as an endocrine disruptor that affects various hormones even at merely physiological levels. We demonstrated recently that BPA binds strongly to human nuclear receptor estrogen-related receptor γ (ERRγ), one of 48 nuclear receptors. Based on X-ray crystal analysis of the ERRγ ligand-binding domain (LBD)/BPA complex, we demonstrated that ERRγ receptor residues, Glu275 and Arg316, function as the intrinsic-binding site of the phenol-hydroxyl group of BPA. If these phenol-hydroxyl↔Glu275 and Arg316 hydrogen bonds anchor the A-benzene ring of BPA, the benzene-phenyl group of BPA would be in a pocket constructed by specific amino acid side chain structures. In the present study, by evaluating the Ala-replaced mutant receptors, we identified such a ligand-binding pocket. Leu268, Leu271, Leu309 and Tyr326, in addition to the previously reported participants Glu275 and Arg316, were found to make a receptacle pocket for the A-ring, whereas Ile279, Ile310 and Val313 were found to assist or structurally support these residues. The results revealed that each amino acid residue is an essential structural element for the strong binding of BPA to ERRγ.

Original languageEnglish
Pages (from-to)403-415
Number of pages13
JournalJournal of biochemistry
Volume151
Issue number4
DOIs
Publication statusPublished - Apr 1 2012

Fingerprint

Cytoplasmic and Nuclear Receptors
Phenol
Estrogen Receptors
Estrogens
Benzene
Ligands
Endocrine Disruptors
Amino Acids
bisphenol A
Anchors
Hydroxyl Radical
Hydrogen
Hydrogen bonds
Binding Sites
X-Rays
Hormones
X rays
Crystals

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Fine spatial assembly for construction of the phenol-binding pocket to capture bisphenol a in the human nuclear receptor estrogen-related receptor γ. / Liu, Xiaohui; Matsushima, Ayami; Nakamura, Masayuki; Costa, Tommaso; Nose, Takeru; Shimohigashi, Yasuyuki.

In: Journal of biochemistry, Vol. 151, No. 4, 01.04.2012, p. 403-415.

Research output: Contribution to journalArticle

@article{05dcb5e4c6c84692ac198e36a695e9e8,
title = "Fine spatial assembly for construction of the phenol-binding pocket to capture bisphenol a in the human nuclear receptor estrogen-related receptor γ",
abstract = "Various lines of evidence have shown that bisphenol A (BPA) acts as an endocrine disruptor that affects various hormones even at merely physiological levels. We demonstrated recently that BPA binds strongly to human nuclear receptor estrogen-related receptor γ (ERRγ), one of 48 nuclear receptors. Based on X-ray crystal analysis of the ERRγ ligand-binding domain (LBD)/BPA complex, we demonstrated that ERRγ receptor residues, Glu275 and Arg316, function as the intrinsic-binding site of the phenol-hydroxyl group of BPA. If these phenol-hydroxyl↔Glu275 and Arg316 hydrogen bonds anchor the A-benzene ring of BPA, the benzene-phenyl group of BPA would be in a pocket constructed by specific amino acid side chain structures. In the present study, by evaluating the Ala-replaced mutant receptors, we identified such a ligand-binding pocket. Leu268, Leu271, Leu309 and Tyr326, in addition to the previously reported participants Glu275 and Arg316, were found to make a receptacle pocket for the A-ring, whereas Ile279, Ile310 and Val313 were found to assist or structurally support these residues. The results revealed that each amino acid residue is an essential structural element for the strong binding of BPA to ERRγ.",
author = "Xiaohui Liu and Ayami Matsushima and Masayuki Nakamura and Tommaso Costa and Takeru Nose and Yasuyuki Shimohigashi",
year = "2012",
month = "4",
day = "1",
doi = "10.1093/jb/mvs008",
language = "English",
volume = "151",
pages = "403--415",
journal = "Journal of Biochemistry",
issn = "0021-924X",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Fine spatial assembly for construction of the phenol-binding pocket to capture bisphenol a in the human nuclear receptor estrogen-related receptor γ

AU - Liu, Xiaohui

AU - Matsushima, Ayami

AU - Nakamura, Masayuki

AU - Costa, Tommaso

AU - Nose, Takeru

AU - Shimohigashi, Yasuyuki

PY - 2012/4/1

Y1 - 2012/4/1

N2 - Various lines of evidence have shown that bisphenol A (BPA) acts as an endocrine disruptor that affects various hormones even at merely physiological levels. We demonstrated recently that BPA binds strongly to human nuclear receptor estrogen-related receptor γ (ERRγ), one of 48 nuclear receptors. Based on X-ray crystal analysis of the ERRγ ligand-binding domain (LBD)/BPA complex, we demonstrated that ERRγ receptor residues, Glu275 and Arg316, function as the intrinsic-binding site of the phenol-hydroxyl group of BPA. If these phenol-hydroxyl↔Glu275 and Arg316 hydrogen bonds anchor the A-benzene ring of BPA, the benzene-phenyl group of BPA would be in a pocket constructed by specific amino acid side chain structures. In the present study, by evaluating the Ala-replaced mutant receptors, we identified such a ligand-binding pocket. Leu268, Leu271, Leu309 and Tyr326, in addition to the previously reported participants Glu275 and Arg316, were found to make a receptacle pocket for the A-ring, whereas Ile279, Ile310 and Val313 were found to assist or structurally support these residues. The results revealed that each amino acid residue is an essential structural element for the strong binding of BPA to ERRγ.

AB - Various lines of evidence have shown that bisphenol A (BPA) acts as an endocrine disruptor that affects various hormones even at merely physiological levels. We demonstrated recently that BPA binds strongly to human nuclear receptor estrogen-related receptor γ (ERRγ), one of 48 nuclear receptors. Based on X-ray crystal analysis of the ERRγ ligand-binding domain (LBD)/BPA complex, we demonstrated that ERRγ receptor residues, Glu275 and Arg316, function as the intrinsic-binding site of the phenol-hydroxyl group of BPA. If these phenol-hydroxyl↔Glu275 and Arg316 hydrogen bonds anchor the A-benzene ring of BPA, the benzene-phenyl group of BPA would be in a pocket constructed by specific amino acid side chain structures. In the present study, by evaluating the Ala-replaced mutant receptors, we identified such a ligand-binding pocket. Leu268, Leu271, Leu309 and Tyr326, in addition to the previously reported participants Glu275 and Arg316, were found to make a receptacle pocket for the A-ring, whereas Ile279, Ile310 and Val313 were found to assist or structurally support these residues. The results revealed that each amino acid residue is an essential structural element for the strong binding of BPA to ERRγ.

UR - http://www.scopus.com/inward/record.url?scp=84859317149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859317149&partnerID=8YFLogxK

U2 - 10.1093/jb/mvs008

DO - 10.1093/jb/mvs008

M3 - Article

VL - 151

SP - 403

EP - 415

JO - Journal of Biochemistry

JF - Journal of Biochemistry

SN - 0021-924X

IS - 4

ER -