title: Noncovalent interaction of oxytetracycline with the enzyme trypsin.
abstract: Oxytetracycline (OTC) is a kind of widely used veterinary drugs. The residue of OTC in the environment (e.g., animal food, soils, surface, and groundwater) is potentially harmful. In this article, the binding mode of OTC with trypsin was investigated using spectroscopic and molecular docking methods. OTC can interact with trypsin with one binding site to form OTC-trypsin complex, resulting in inhibition of trypsin activity and change of the secondary structure and the microenvironment of the tryptophan residues of trypsin. After elimination of the inner filter effect, the association constant, K, was calculated to be K(290K) = 1.36 × 10(5) L mol(-1), K(298K) = 7.30 × 10(4) L mol(-1), and K(307K) = 3.58 × 10(4) L mol(-1) at three different temperatures. The calculated thermodynamic parameters (negative values of ΔH(○) and ΔS(○)) indicated that van der Waals interactions and hydrogen bonds play a major role during the interaction. The molecular docking study revealed that OTC bound into the S1 binding pocket, which illustrates that the trypsin activity was competitively inhibited by OTC, in accordance with the conclusion of the trypsin activity experiment. This work establishes a new strategy to probe the toxicity of OTC and contributes to clarify its molecular mechanism of toxicity in vivo. The combination of spectroscopic and molecular docking methods in this work can be applied to investigate the potential enzyme toxicity of other small organic pollutants and drugs.
authors.affiliation: Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, China-America CRC for Environment & Health, Shandong Province, 27# Shanda South Road, Jinan 250100, P.R. China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Chi
authors.forename: Rutao
authors.initials: R
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D004347:Drug Interactions; D005453:Fluorescence; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D010118:Oxytetracycline / Q000737:chemistry* / Q000378:metabolism*; D010179:Pancreas / Q000201:enzymology; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics; D014357:Trypsin / Q000737:chemistry* / Q000378:metabolism*; D019155:Veterinary Drugs / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D019155:Veterinary Drugs; D014357:Trypsin; D010118:Oxytetracycline