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

DOI: 10.1021/acs.biochem.7b00041 DOI Help

Authors: Nikolette L. Mccombs (North Carolina State University) , Tadeo Moreno Chicano (University of Essex) , Leiah M. Carey (North Carolina State University) , Stefan Franzen (North Carolina State University) , Michael A. Hough (University of Essex) , Reza A. Ghiladi (North Carolina State University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochemistry

State: Published (Approved)
Published: April 2017
Diamond Proposal Number(s): 13467

Abstract: 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. UV-visible and resonance Raman spectroscopic studies showed an increase in the 6-coordinate low spin heme population in DHP isoenzyme B upon binding of imidazole, benzotriazole, and benzimidazole (Kd values = 52, 82, and 110 M, 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 (1.06 Å), and indazole (1.12 Å) revealed two ligand binding motifs, one with direct ligand binding to the heme-Fe, and another where 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 increasing our understanding of their impact on infaunal organisms in marine and aquatic environments.

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)