8w5z

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

spinqualitylabelsall models 8w5z, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8w5z is a 4 chain structure with sequence from Ixodes and Longicornis species complex. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: 1PS, A3P, MG, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B7Q097_IXOSC Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3'-phosphoadenylyl sulfate (PAPS) as cosubstrate.[RuleBase:RU365018] Publication Abstract from PubMed 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. Crystal structure of tick tyrosylprotein sulfotransferase reveals the activation mechanism of the tick anticoagulant protein madanin.,Yoshimura M, Teramoto T, Asano H, Iwamoto Y, Kondo M, Nishimoto E, Kakuta Y J Biol Chem. 2024 Mar;300(3):105748. doi: 10.1016/j.jbc.2024.105748. Epub 2024 , Feb 13. PMID:38354785 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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