Tyrosine-O-sulfation is a common post-translational modification (PTM) of proteins following the cellular secretory pathway. First described in human fibrinogen, tyrosine-O-sulfation has long been associated with the modulation of protein–protein interactions in several physiological processes. A number of relevant interactions for hemostasis are largely dictated by this PTM, many of which involving the serine proteinase thrombin (FIIa), a central player in the blood-clotting cascade. Tyrosine sulfation is not limited to endogenous FIIa ligands and has also been found in hirudin, a well-known and potent thrombin inhibitor from the medicinal leech, Hirudo medicinalis. The discovery of hirudin led to successful clinical application of analogs of leech-inspired molecules, but also unveiled several other natural thrombin-directed anticoagulant molecules, many of which undergo tyrosine-O-sulfation. The presence of this PTM has been shown to enhance the anticoagulant properties of these peptides from a range of blood-feeding organisms, including ticks, mosquitos and flies. Interestingly, some of these molecules display mechanisms of action that mimic those of thrombin's bona fide substrates.
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February 2022
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The highly conserved enzyme IMPDH plays an essential role in purine biosynthesis and is tightly regulated by many different mechanisms. Depicted here are cryo-EM structures of the large retinal splice variant of IMPDH1 in different filament assembly conformations overlaid on a cryo-EM micrograph of IMPDH1 filaments. Cover artwork created by Jesse Hansen.
Review Article|
January 07 2022
Tyrosine-O-sulfation is a widespread affinity enhancer among thrombin interactors
Jorge Ripoll-Rozada
;
1IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal
2Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
Correspondence: Jorge Ripoll-Rozada (jorge.rozada@ibmc.up.pt)
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Joshua W. C. Maxwell;
Joshua W. C. Maxwell
3School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia
4Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney, Sydney, New South Wales 2006, Australia
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Richard J. Payne;
Richard J. Payne
3School of Chemistry, The University of Sydney, Sydney, New South Wales 2006, Australia
4Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney, Sydney, New South Wales 2006, Australia
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Pedro José Barbosa Pereira
Pedro José Barbosa Pereira
1IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal
2Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
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Publisher: Portland Press Ltd
Received:
September 16 2021
Revision Received:
December 07 2021
Accepted:
December 09 2021
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem Soc Trans (2022) 50 (1): 387–401.
Article history
Received:
September 16 2021
Revision Received:
December 07 2021
Accepted:
December 09 2021
Citation
Jorge Ripoll-Rozada, Joshua W. C. Maxwell, Richard J. Payne, Pedro José Barbosa Pereira; Tyrosine-O-sulfation is a widespread affinity enhancer among thrombin interactors. Biochem Soc Trans 28 February 2022; 50 (1): 387–401. doi: https://doi.org/10.1042/BST20210600
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