@article{68e7292048834cd6b83789c1f5149be2,
title = "Tyrosine Sulfation Restricts the Conformational Ensemble of a Flexible Peptide, Strengthening the Binding Affinity for an Antibody",
abstract = "Protein tyrosine sulfation (PTS) is a post-translational modification regulating numerous biological events. PTS generally occurs at flexible regions of proteins, enhancing intermolecular interactions between proteins. Because of the high flexibility associated with the regions where PTS is generally encountered, an atomic-level understanding has been difficult to achieve by X-ray crystallography or nuclear magnetic resonance techniques. In this study, we focused on the conformational behavior of a flexible sulfated peptide and its interaction with an antibody. Molecular dynamics simulations and thermodynamic analysis indicated that PTS reduced the main-chain fluctuations upon the appearance of sulfate-mediated intramolecular H-bonds. Collectively, our data suggested that one of the mechanisms by which PTS may enhance protein-protein interactions consists of the limitation of conformational dynamics in the unbound state, thus reducing the loss of entropy upon binding and boosting the affinity for its partner.",
author = "Kazuhiro Miyanabe and Takefumi Yamashita and Yoshito Abe and Hiroki Akiba and Yuichiro Takamatsu and Makoto Nakakido and Takao Hamakubo and Tadashi Ueda and Caaveiro, {Jose M.M.} and Kouhei Tsumoto",
note = "Funding Information: This work was supported by the Funding program for World-Leading Innovative R&D on Science and Technology (FIRST) from JSPS and by JSPS Grants-in-Aid for Scientific Research 25249115 (K.T.), 15K06962 (J.M.M.C.), 15H05752 and 15KT0103 (T.Y.) and SIP Project SM4I (T.Y.). Funding Information: *E-mail: jose@phar.kyushu-u.ac.jp. *E-mail: tsumoto@bioeng.t.u-tokyo.ac.jp. ORCID Yoshito Abe: 0000-0002-0016-8490 Jose M. M. Caaveiro: 0000-0001-5568-2369 Author Contributions K.M. designed research, performed experiments (protein purification, ITC, MD simulations, and crystallization), analyzed and discussed the results, and wrote the manuscript. T.Y. designed research, analyzed and discussed the results, and contributed new computational tools and models. Y.A. designed research, performed NMR experiments, and analyzed that data. H.A. analyzed and discussed the results. Y.T. contributed new computational tools. M.N. analyzed and discussed the results. T.H. contributed new reagents and materials. T.U. designed research. J.M.M.C. designed research, performed experiments (crystal manipulation and crystallographic data collection and processing), analyzed and discussed the results, and wrote the manuscript. K.T. designed the overall study, designed research, analyzed and discussed the results, and made critical revisions to the manuscript. Funding This work was supported by the Funding program for world-leading Innovative R&D on Science and Technology (FIRST) from JSPS and by JSPS Grants-in-Aid for Scientific Research 25249115 (K.T.), 15K06962 (J.M.M.C.), 15H05752, and 15KT0103 (T.Y.) and SIP Project SM4I (T.Y.). Notes The authors declare no competing financial interest.",
year = "2018",
month = jul,
day = "17",
doi = "10.1021/acs.biochem.8b00592",
language = "English",
volume = "57",
pages = "4177--4185",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "28",
}