Terpyridine Platinum(II) Complexes Inhibit Cysteine Proteases by Binding to Active-site Cysteine |
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| Authors: | Yan-Chung Lo Wen-Chi Su Tzu-Ping Ko Nai-Chen Wang Andrew H-J Wang |
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| Institution: | 1. Department and Institute of Pharmacology, National Yang-Ming University , Taipei , 112 , Taiwan;2. Institute of Biological Chemistry;3. Institute of Molecular Biology;4. Institute of Biological Chemistry;5. National Core Facility of High-Throughput Protein Crystallography , Academia Sinica, Taipei , 115 , Taiwan;6. Institute of Biological Chemistry |
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| Abstract: | Abstract Platinum(II) complexes have been demonstrated to form covalent bonds with sulfur-donating ligands (in glutathione, metallothionein and other sulfur-containing biomolecules) or coordination bonds with nitrogen-donating ligands (such as histidine and guanine). To investigate how these compounds interact with cysteine proteases, we chose terpyridine platinum(II) (TP-Pt(II)) complexes as a model system. By using X-ray crystallography, we demonstrated that TP-Pt(II) formed a covalent bond with the catalytic cysteine residue in pyroglutamyl peptidase I. Moreover, by using MALDI (matrix-assisted laser desorption/ionization) and TOF-TOF (time of flight) mass spectrometry, we elucidated that the TP-Pt(II) complex formed a covalent bond with the active-site cysteine residue in two other types of cysteine protease. Taken together, the results unequivocally showed that TP-Pt(II) complexes can selectively bind to the active site of most cysteine proteases. Our findings here can be useful in the design of new anti-cancer, anti-parasite or anti-virus platinum(II) compounds. |
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| Keywords: | Platinum(II) Enzyme activity Cysteine protease inhibitors Crystal structure |
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