Crystal structure of tick tyrosylprotein sulfotransferase reveals the activation mechanism of the tick anticoagulant protein madanin.

Autor:	Yoshimura M; Faculty of Agriculture, Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Kyushu University, Fukuoka, Japan., Teramoto T; Faculty of Agriculture, Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Kyushu University, Fukuoka, Japan. Electronic address: teramotot@agr.kyushu-u.ac.jp., Asano H; Faculty of Agriculture, Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Kyushu University, Fukuoka, Japan., Iwamoto Y; Faculty of Agriculture, Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Kyushu University, Fukuoka, Japan., Kondo M; Faculty of Agriculture, Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Kyushu University, Fukuoka, Japan., Nishimoto E; Faculty of Agriculture, Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Kyushu University, Fukuoka, Japan., Kakuta Y; Faculty of Agriculture, Laboratory of Biophysical Chemistry, Department of Bioscience and Biotechnology, Kyushu University, Fukuoka, Japan. Electronic address: kakuta@agr.kyushu-u.ac.jp.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Mar; Vol. 300 (3), pp. 105748. Date of Electronic Publication: 2024 Feb 13.
DOI:	10.1016/j.jbc.2024.105748
Abstrakt:	Ticks pose a substantial public health risk as they transmit various pathogens. This concern is related to the adept blood-sucking strategy of ticks, underscored by the action of the anticoagulant, madanin, which is known to exhibit an approximately 1000-fold increase in anticoagulant activity following sulfation of its two tyrosine residues, Tyr51 and Tyr54. Despite this knowledge, the molecular mechanism underlying sulfation by tick tyrosylprotein sulfotransferase (TPST) remains unclear. In this study, we successfully prepared tick TPST as a soluble recombinant enzyme. We clarified the method by which this enzyme proficiently sulfates tyrosine residues in madanin. Biochemical analysis using a substrate peptide based on madanin and tick TPST, along with the analysis of the crystal structure of the complex and docking simulations, revealed a sequential sulfation process. Initial sulfation at the Tyr51 site augments binding, thereby facilitating efficient sulfation at Tyr54. Beyond direct biochemical implications, these findings considerably improve our understanding of tick blood-sucking strategies. Furthermore, combined with the utility of modified tick TPST, our findings may lead to the development of novel anticoagulants, promising avenues for thrombotic disease intervention and advancements in the field of public health. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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