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Interaction of Azole-Based Environmental Pollutants with the Coelomic Hemoglobin from Amphitrite ornata: A Molecular Basis for Toxicity

McCombs, NL and Moreno-Chicano, T and Carey, LM and Franzen, S and Hough, MA and Ghiladi, RA (2017) 'Interaction of Azole-Based Environmental Pollutants with the Coelomic Hemoglobin from Amphitrite ornata: A Molecular Basis for Toxicity.' Biochemistry, 56 (17). pp. 2294-2303. ISSN 0006-2960

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The toxicities of azole pollutants that have widespread agricultural and industrial uses are either poorly understood or unknown, particularly with respect to how infaunal organisms are impacted by this class of persistent organic pollutant. To identify a molecular basis by which azole compounds may have unforeseen toxicity on marine annelids, we examine here their impact on the multifunctional dehaloperoxidase (DHP) hemoglobin from the terebellid polychaete Amphitrite ornata. Ultraviolet-visible and resonance Raman spectroscopic studies showed an increase in the six-coordinate low-spin heme population in DHP isoenzyme B upon binding of imidazole, benzotriazole, and benzimidazole (K d values of 52, 82, and 110 μM, respectively), suggestive of their direct binding to the heme-Fe. Accordingly, atomic-resolution X-ray crystal structures, supported by computational studies, of the DHP B complexes of benzotriazole (1.14 Å), benzimidazole (1.08 Å), imidazole (1.08 Å), and indazole (1.12 Å) revealed two ligand binding motifs, one with direct ligand binding to the heme-Fe, and another in which the ligand binds in the hydrophobic distal pocket without coordinating the heme-Fe. Taken together, the results demonstrate a new mechanism by which azole pollutants can potentially disrupt hemoglobin function, thereby improving our understanding of their i mpact on infaunal organisms in marine and aquatic environments.

Item Type: Article
Uncontrolled Keywords: Animals; Polychaeta; Triazoles; Imidazoles; Indazoles; Benzimidazoles; Isoenzymes; Peroxidases; Hemoglobins; Recombinant Proteins; Recombinant Fusion Proteins; Enzyme Inhibitors; Ligands; Pesticides; Fungicides, Industrial; Environmental Pollutants; Computational Biology; Amino Acid Motifs; Catalytic Domain; Kinetics; Hydrogen Bonding; Models, Molecular; Hydrophobic and Hydrophilic Interactions
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 29 Jun 2017 14:16
Last Modified: 18 Aug 2022 11:23

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