Structural studies on inhibitory mechanisms of antibiotic, corticosteroid and catecholamine molecules on lactoperoxidase.

Autor: Sheikh IA; King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: iasheikh@kau.edu.sa., Jiffri EH; Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Ashraf GM; King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Kamal MA; King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Beg MA; King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2018 Aug 15; Vol. 207, pp. 412-419. Date of Electronic Publication: 2018 Jun 25.
DOI: 10.1016/j.lfs.2018.06.027
Abstrakt: Aim: Lactoperoxidase (LPO) is an essential protein with broad spectrum antimicrobial activity present in mammalian milk. It imparts immunity to infants against wide range of pathogenic infections. Several in vitro studies have shown inhibition of LPO activity by pharmaceutical compounds including commonly used antibiotics such as ampicillin and gentamicin, and molecules like prednisolone, norepinephrine, etc. Prescription of such drugs to lactating mothers might have adverse health effects on infants. The aim of our study was the elucidation of the structural aspects of the inhibitory mechanism of ampicillin, gentamicin, amoxicillin, prednisolone and norepinephrine on LPO.
Material and Methods: Three dimensional structure of camel LPO (cLPO) was developed using homology modeling and used for in silico experimental studies. The Schrödinger induced fit docking along with binding affinity estimation experiments were performed. The cLPO and Ligands were prepared using Protein Preparation Wizard and Ligprep modules available in Schrodinger suite. For estimating Binding affinity Prime Molecular Mechanics with Generalized Born and Surface Area (MMGB-SA) module was used.
Key Results: The five drug ligands formed three to five hydrogen bonding interactions with cLPO. Amino acids Arg-231, Asp-232, Ser-370, Arg-371 and Glu-374 of cLPO were crucial for these interactions. The binding affinity values for gentamicin were highest and for norepinephrine were the lowest.
Significance: This study concludes that the five drug molecules show potential ability to inhibit the LPO activity. Further, a very high sequence similarity of cLPO with human LPO imparts high significance to these conclusions in relation to human health especially in new born infants.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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