6uxu | pdb_00006uxu

X-ray Crystal Structure of Chlorothalonil Dehalogenase: Analyzing the Catalytic Mechanism of Hydrolytic Dehalogenation

spinqualitylabelsall models 6uxu, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6uxu is a 2 chain structure with sequence from Ochrobactrum sp. ctn-1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Gene: chd (Ochrobactrum sp. CTN-1) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Cleavage of aromatic carbon-chlorine bonds is critical for the degradation of toxic industrial compounds. Here, we solved the X-ray crystal structure of chlorothalonil dehalogenase (Chd) from Pseudomonas sp. CTN-3, with 15 of its N-terminal residues truncated (ChdT), using single-wavelength anomalous dispersion refined to 1.96 A resolution. Chd has low sequence identity (< 15%) compared with all other proteins whose structures are currently available, and to the best of our knowledge, we present the first structure of a Zn(II)-dependent aromatic dehalogenase that does not require a coenzyme. ChdT forms a "head-to-tail" homodimer, formed between two alpha-helices from each monomer, with three Zn(II)-binding sites, two of which occupy the active sites, while the third anchors a structural site at the homodimer interface. The catalytic Zn(II) ions are solvent-accessible via a large hydrophobic (8.5 x 17.8 A) opening to bulk solvent and two hydrophilic branched channels. Each active-site Zn(II) ion resides in a distorted trigonal bipyramid geometry with His-117, His-257, Asp-116, Asn-216, and a water/hydroxide as ligands. A conserved His residue, His-114, is hydrogen-bonded to the Zn(II)-bound water/hydroxide and likely functions as the general acid-base. We examined substrate binding by docking chlorothalonil (TPN) into the hydrophobic channel and observed that the most energetically favorable pose includes a TPN orientation that coordinates to the active-site Zn(II) ions via a CN and that maximizes a pi-pi interaction with Trp-227. On the basis of these results, along with previously reported kinetics data, we propose a refined catalytic mechanism for Chd-mediated TPN dehalogenation. Structural basis for the hydrolytic dehalogenation of the fungicide chlorothalonil.,Catlin DS, Yang X, Bennett B, Holz RC, Liu D J Biol Chem. 2020 Apr 30. pii: RA120.013150. doi: 10.1074/jbc.RA120.013150. PMID:32358058 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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