3buz

Crystal structure of ia-bTAD-actin complex

spinqualitylabelsall models 3buz, resolution 2.81Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3buz is a 2 chain structure with sequence from "bacillus_perfringens"_veillon_and_zuber_1898 "bacillus perfringens" veillon and zuber 1898 and European rabbit. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ATP, CA, LAR, TAD Gene: ACTA1, ACTA (European rabbit) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The ADP-ribosylating toxins (ADPRTs) produced by pathogenic bacteria modify intracellular protein and affect eukaryotic cell function. Actin-specific ADPRTs (including Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin) ADP-ribosylate G-actin at Arg-177, leading to disorganization of the cytoskeleton and cell death. Although the structures of many actin-specific ADPRTs are available, the mechanisms underlying actin recognition and selective ADP-ribosylation of Arg-177 remain unknown. Here we report the crystal structure of actin-Ia in complex with the nonhydrolyzable NAD analog betaTAD at 2.8 A resolution. The structure indicates that Ia recognizes actin via five loops around NAD: loop I (Tyr-60-Tyr-62 in the N domain), loop II (active-site loop), loop III, loop IV (PN loop), and loop V (ADP-ribosylating turn-turn loop). We used site-directed mutagenesis to confirm that loop I on the N domain and loop II are essential for the ADP-ribosyltransferase activity. Furthermore, we revealed that Glu-378 on the EXE loop is in close proximity to Arg-177 in actin, and we proposed that the ADP-ribosylation of Arg-177 proceeds by an SN1 reaction via first an oxocarbenium ion intermediate and second a cationic intermediate by alleviating the strained conformation of the first oxocarbenium ion. Our results suggest a common reaction mechanism for ADPRTs. Moreover, the structure might be of use in rational drug design to block toxin-substrate recognition. Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfringens iota-toxin.,Tsuge H, Nagahama M, Oda M, Iwamoto S, Utsunomiya H, Marquez VE, Katunuma N, Nishizawa M, Sakurai J Proc Natl Acad Sci U S A. 2008 May 27;105(21):7399-404. Epub 2008 May 19. PMID:18490658 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Actin 3D structures

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