title: 3D Structure, Dimerization Modeling, and Lead Discovery by Ligand-protein Interaction Analysis of p60 Transcription Regulator Protein (p60TRP).
abstract: The p60 transcription regulator protein (p60TRP) is a basic helix-loop-helix (bHLH) domain-containing neuroprotective protein and a member of the G-protein-coupled receptor (GPCR)-associated sorting protein (GPRASP) family. In the present study, multiple theoretical physico-chemical methods (e.g. Modeller v.9.13, I-TASSER, PROCHECK and ClusPro v2.0 with PIPER) were applied to unveil the three-dimensional (3D) protein structure of the p60TRP homo-dimer protein and explore potential ligand-protein interactions. Our results suggest a Mg(2+) -containing 3D p60TRP dimer protein that potentially interacts with 5-(1-aziridinyl)-2,4-dinitrobenzamide (CB1954) and [2-(3-dodecylimidazolidin-1-yl)-1-phosphonoethyl] phosphonic acid (B73). The discovery of CB1954 and B73 may serve as a potential lead for further drug screening tests to normalize the p60TRP signaling pathway in neurodegenerative diseases. Interference with p60TRP signaling via CB1954/B73-related molecules might be a novel option for modifying neurodegenerative signaling pathways (e.g. RIN1, PP2A, RanBP5, CREB and SYNJ1) to treat various brain diseases.
authors: Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea, Tel.: + 82 2 2220 0398.
authors: Subrata
authors: S
authors: Pramanik
authors: Department of Information Systems, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea.
authors: Arne
authors: A
authors: Kutzner
authors: Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Republic of Korea, Tel.: + 82 2 2220 0398. klaus.heese@rub.de, klaus@hanyang.ac.kr.
authors: Klaus
authors: K
authors: Heese
mesh_terms: D000818:Animals; D001388:Aziridines / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001388:Aziridines; D051792:Basic Helix-Loop-Helix Proteins; C100099:tretazicar
keywords: Alzheimer’s disease; BHLHB9; brain; in silico; interaction; lead discovery; p60TRP