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Crimean Congo Hemorrhagic Fever Virus OTU domain in complex with ubiquitin-propargyl.Crimean Congo Hemorrhagic Fever Virus OTU domain in complex with ubiquitin-propargyl.
Structural highlights
Publication Abstract from PubMedActive-site directed probes are powerful in studies of enzymatic function. We report an active-site directed probe based on a warhead so far considered unreactive. By replacing the C-terminal carboxylate of ubiquitin (Ub) with an alkyne functionality, a selective reaction with the active-site cysteine residue of de-ubiquitinating enzymes was observed. The resulting product was shown to be a quaternary vinyl thioether, as determined by X-ray crystallography. Proteomic analysis of proteins bound to an immobilized Ub alkyne probe confirmed the selectivity toward de-ubiquitinating enzymes. The observed reactivity is not just restricted to propargylated Ub, as highlighted by the selective reaction between caspase-1 (interleukin converting enzyme) and a propargylated peptide derived from IL-1beta, a caspase-1 substrate. On Terminal Alkynes That Can React with Active-Site Cysteine Nucleophiles in Proteases.,Ekkebus R, van Kasteren SI, Kulathu Y, Scholten A, Berlin I, Geurink PP, de Jong A, Goerdayal S, Neefjes J, Heck AJ, Komander D, Ovaa H J Am Chem Soc. 2013 Feb 15. PMID:23387960[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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