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.
authors: Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors: Yasuha
authors: Y
authors: Hori-Tanaka
authors: Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1, Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan; Center for Informational Biology, Ochanomizu University, 2-1-1, Otsuka, Bunkyo-ku, Tokyo 112-8610, Japan; National Institute of Genetics, 1111, Yata, Mishima, Shizuoka 411-8540, Japan. Electronic address: yura.kei@ocha.ac.jp.
authors: Kei
authors: K
authors: Yura
authors: Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Tohoku Medical Megabank Organization, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8573, Japan.
authors: Takako
authors: T
authors: Takai-Igarashi
authors: Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Tohoku Medical Megabank Organization, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8573, Japan.
authors: Hiroshi
authors: H
authors: Tanaka
mesh_terms: D001665:Binding Sites; D030562:Databases, Protein; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013256:Steroids / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D011506:Proteins; D013256:Steroids
keywords: Function-unknown protein; Principle component analysis; Side effect; Structural bioinformatics; Three-dimensional structure