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 Clostridium perfringens and Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.81Å Ligands: ATP, CA, LAR, TAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q46220_CLOPF 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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