Positively-Charged Semi-Tunnel Is a Structural and Surface Characteristic of Polyphosphate-Binding Proteins: An In-Silico Study

• Authors: Zheng Zachory Wei, Emory University; Greg Vatcher, Peking University; Alvin Hok Yan Tin, Peking University; Jun Lin Teng, Peking University; Juan Wang, Peking University; Qing Hua Cui, Peking University; Jian Guo Chen, Peking University; Albert Cheung Hoi Yu, Peking University
• Journal Title: PLoS ONE
• Volume: Volume 10, Number 4
• Publisher: Public Library of Science | 2015-04-16, Pages e0123713-e0123713
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0123713
• Subjects: Engineering, Biomedical; Biology, Molecular
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; INORGANIC POLYPHOSPHATE; CRYSTAL-STRUCTURE; EXOPOLYPHOSPHATASE; KINASE; IDENTIFICATION; PHOSPHATASE; METABOLISM; EUKARYOTE; ALIGNMENT; COMPLEX

Abstract

Phosphate is essential for all major life processes, especially energy metabolism and signal transduction. A linear phosphate polymer, polyphosphate (polyP), linked by high-energy phosphoanhydride bonds, can interact with various proteins, playing important roles as an energy source and regulatory factor. However, polyP-binding structures are largely unknown. Here we proposed a putative polyP binding site, a positively-charged semi-tunnel (PCST), identified by surface electrostatics analyses in polyP kinases (PPKs) and many other polyP-related proteins.We found that the PCSTs in varied proteins were folded in different secondary structure compositions. Molecular docking calculations revealed a significant value for binding affinity to polyP in PCST-containing proteins. Utilizing the PCST identified in the β subunit of PPK3, we predicted the potential polyP-binding domain of PPK3. The discovery of this feature facilitates future searches for polyP-binding proteins and discovery of the mechanisms for polyP-binding activities. This should greatly enhance the understanding of the many physiological functions of protein-bound polyP and the involvement of polyP and polyP-binding proteins in various human diseases.