Structural classification of steroid-binding sites on proteins by coarse-grained atomic environment and its correlation with their biological function

Yasuha Hori-Tanaka, Kei Yura, Takako Takai-Igarashi, Hiroshi Tanaka

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Steroid hormone is extensively used for transmitting variety of biological signals in organisms. Natural steroid hormone is synthesized from cholesterol in adrenal cortex and in sexual gland in vertebrates. Appropriately dosed synthetic steroid hormones can be used for medication. Despite their positive effects as medicine, they sometimes cause significant side effects due to their wide range of actions, and the studies for discovering the mechanisms of side effects were carried out aiming to reduce the side effects. The fundamental cause of the side effects seems to be interactions between the steroid and a non-target protein. To understand the possible range of interaction of steroid molecule, we gathered all the three-dimensional structures of protein-steroid complex determined by X-ray crystallography, compared the atomic environments of the steroid-binding sites in proteins and classified the pattern of steroid binding. Protein Data Bank contained 871 structures of steroid-protein complexes in 382 entries. For this study, we selected 832 steroid binding proteins. Using a newly developed method to describe the atomic environments of these steroid molecules and their function, we were able to separate the environments into six patterns. This classification had a potential to predict the function of function-unknown proteins with a co-crystallized steroid molecule. We speculated that the proteins grouped into the same pattern of nuclear receptors were the candidates of non-targeted proteins causing a side effect by a therapeutic prescription of steroid hormone.

Original languageEnglish
Pages (from-to)81-88
Number of pages8
JournalSteroids
Volume96
DOIs
Publication statusPublished - 2015
Externally publishedYes

Fingerprint

Steroids
Binding Sites
Steroid hormones
Proteins
Hormones
Molecules
X ray crystallography
Cytoplasmic and Nuclear Receptors
Medicine
Carrier Proteins
Adrenal Cortex
X Ray Crystallography
Cholesterol
Therapeutic Uses
Prescriptions
Vertebrates
Databases

Keywords

  • Function-unknown protein
  • Principle component analysis
  • Side effect
  • Structural bioinformatics
  • Three-dimensional structure

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology
  • Medicine(all)

Cite this

Structural classification of steroid-binding sites on proteins by coarse-grained atomic environment and its correlation with their biological function. / Hori-Tanaka, Yasuha; Yura, Kei; Takai-Igarashi, Takako; Tanaka, Hiroshi.

In: Steroids, Vol. 96, 2015, p. 81-88.

Research output: Contribution to journalArticle

@article{9b203291fb1c43f299abdc442cd9776c,
title = "Structural classification of steroid-binding sites on proteins by coarse-grained atomic environment and its correlation with their biological function",
abstract = "Steroid hormone is extensively used for transmitting variety of biological signals in organisms. Natural steroid hormone is synthesized from cholesterol in adrenal cortex and in sexual gland in vertebrates. Appropriately dosed synthetic steroid hormones can be used for medication. Despite their positive effects as medicine, they sometimes cause significant side effects due to their wide range of actions, and the studies for discovering the mechanisms of side effects were carried out aiming to reduce the side effects. The fundamental cause of the side effects seems to be interactions between the steroid and a non-target protein. To understand the possible range of interaction of steroid molecule, we gathered all the three-dimensional structures of protein-steroid complex determined by X-ray crystallography, compared the atomic environments of the steroid-binding sites in proteins and classified the pattern of steroid binding. Protein Data Bank contained 871 structures of steroid-protein complexes in 382 entries. For this study, we selected 832 steroid binding proteins. Using a newly developed method to describe the atomic environments of these steroid molecules and their function, we were able to separate the environments into six patterns. This classification had a potential to predict the function of function-unknown proteins with a co-crystallized steroid molecule. We speculated that the proteins grouped into the same pattern of nuclear receptors were the candidates of non-targeted proteins causing a side effect by a therapeutic prescription of steroid hormone.",
keywords = "Function-unknown protein, Principle component analysis, Side effect, Structural bioinformatics, Three-dimensional structure",
author = "Yasuha Hori-Tanaka and Kei Yura and Takako Takai-Igarashi and Hiroshi Tanaka",
year = "2015",
doi = "10.1016/j.steroids.2015.01.015",
language = "English",
volume = "96",
pages = "81--88",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Structural classification of steroid-binding sites on proteins by coarse-grained atomic environment and its correlation with their biological function

AU - Hori-Tanaka, Yasuha

AU - Yura, Kei

AU - Takai-Igarashi, Takako

AU - Tanaka, Hiroshi

PY - 2015

Y1 - 2015

N2 - Steroid hormone is extensively used for transmitting variety of biological signals in organisms. Natural steroid hormone is synthesized from cholesterol in adrenal cortex and in sexual gland in vertebrates. Appropriately dosed synthetic steroid hormones can be used for medication. Despite their positive effects as medicine, they sometimes cause significant side effects due to their wide range of actions, and the studies for discovering the mechanisms of side effects were carried out aiming to reduce the side effects. The fundamental cause of the side effects seems to be interactions between the steroid and a non-target protein. To understand the possible range of interaction of steroid molecule, we gathered all the three-dimensional structures of protein-steroid complex determined by X-ray crystallography, compared the atomic environments of the steroid-binding sites in proteins and classified the pattern of steroid binding. Protein Data Bank contained 871 structures of steroid-protein complexes in 382 entries. For this study, we selected 832 steroid binding proteins. Using a newly developed method to describe the atomic environments of these steroid molecules and their function, we were able to separate the environments into six patterns. This classification had a potential to predict the function of function-unknown proteins with a co-crystallized steroid molecule. We speculated that the proteins grouped into the same pattern of nuclear receptors were the candidates of non-targeted proteins causing a side effect by a therapeutic prescription of steroid hormone.

AB - Steroid hormone is extensively used for transmitting variety of biological signals in organisms. Natural steroid hormone is synthesized from cholesterol in adrenal cortex and in sexual gland in vertebrates. Appropriately dosed synthetic steroid hormones can be used for medication. Despite their positive effects as medicine, they sometimes cause significant side effects due to their wide range of actions, and the studies for discovering the mechanisms of side effects were carried out aiming to reduce the side effects. The fundamental cause of the side effects seems to be interactions between the steroid and a non-target protein. To understand the possible range of interaction of steroid molecule, we gathered all the three-dimensional structures of protein-steroid complex determined by X-ray crystallography, compared the atomic environments of the steroid-binding sites in proteins and classified the pattern of steroid binding. Protein Data Bank contained 871 structures of steroid-protein complexes in 382 entries. For this study, we selected 832 steroid binding proteins. Using a newly developed method to describe the atomic environments of these steroid molecules and their function, we were able to separate the environments into six patterns. This classification had a potential to predict the function of function-unknown proteins with a co-crystallized steroid molecule. We speculated that the proteins grouped into the same pattern of nuclear receptors were the candidates of non-targeted proteins causing a side effect by a therapeutic prescription of steroid hormone.

KW - Function-unknown protein

KW - Principle component analysis

KW - Side effect

KW - Structural bioinformatics

KW - Three-dimensional structure

UR - http://www.scopus.com/inward/record.url?scp=84922514646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922514646&partnerID=8YFLogxK

U2 - 10.1016/j.steroids.2015.01.015

DO - 10.1016/j.steroids.2015.01.015

M3 - Article

VL - 96

SP - 81

EP - 88

JO - Steroids

JF - Steroids

SN - 0039-128X

ER -