3zfo

Crystal structure of substrate-like, unprocessed N-terminal protease Npro mutant S169P

spinqualitylabelsall models 3zfo, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3zfo is a 1 chain structure with sequence from Pestivirus strain d32/00_hobi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, OH, SGM Related: 3zfn, 3zfp, 3zfq, 3zfr, 3zft, 3zfu Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Npro is a key effector protein of pestiviruses such as bovine viral diarrhea virus and abolishes host cell antiviral defense mechanisms. Synthesized as the N-terminal part of the viral polyprotein, Npro releases itself via an autoproteolytic cleavage, triggering its immunological functions. However, the mechanisms of its proteolytic action and its immune escape were unclear. Here, we present the crystal structures of Npro to 1.25 A resolution. Structures of pre- and postcleavage intermediates identify three catalytically relevant elements. The trapping of the putative catalytic water reveals its distinct roles as a base, acid, and nucleophile. The presentation of the substrate further explains the enigmatic latency of the protease, ensuring a single in cis cleavage. Additionally, we identified a zinc-free, disulfide-linked conformation of the TRASH motif, an interaction hub of immune factors. The structure opens additional opportunities in utilizing Npro as an autocleaving fusion protein and as a pharmaceutical target. Crystal Structures of the Viral Protease Npro Imply Distinct Roles for the Catalytic Water in Catalysis.,Zogg T, Sponring M, Schindler S, Koll M, Schneider R, Brandstetter H, Auer B Structure. 2013 Apr 30. pii: S0969-2126(13)00112-3. doi:, 10.1016/j.str.2013.04.003. PMID:23643950 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nonstructural protein

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