3ZNH

Crimean Congo Hemorrhagic Fever Virus OTU domain in complex with ubiquitin-propargyl.

Summary for 3ZNH

• Entry DOI: 10.2210/pdb3znh/pdb
• Descriptor: UBIQUITIN THIOESTERASE, POLYUBIQUITIN-B (3 entities in total)
• Functional Keywords: hydrolase-signaling protein complex, deubiquitinase, hydrolase/signaling protein
• Biological source: CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS; More
• Cellular location: Ubiquitin: Cytoplasm (By similarity): P0CG47
• Total number of polymer chains: 2
• Total formula weight: 29416.27

Authors

Ekkebus, R.,vanKasteren, S.I.,Kulathu, Y.,Scholten, A.,Berlin, I.,deJong, A.,Goerdayal, G.,Neefjes, J.,Heck, A.J.R.,Komander, D.,Ovaa, H. (deposition date: 2013-02-14, release date: 2013-02-27, Last modification date: 2024-10-16)

Primary citation

Ekkebus, R.,Van Kasteren, S.I.,Kulathu, Y.,Scholten, A.,Berlin, I.,Geurink, P.P.,De Jong, A.,Goerdayal, G.,Neefjes, J.,Heck, A.J.R.,Komander, D.,Ovaa, H.
On Terminal Alkynes that Can React with Active-Site Cysteine Nucleophiles in Proteases.
J.Am.Chem.Soc., 135:2867-, 2013

PubMed Abstract: Active-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-1β, a caspase-1 substrate.

PubMed: 23387960
DOI: 10.1021/JA309802N

Experimental method

X-RAY DIFFRACTION (2.3 Å)