摘要

      目标：
      乳过氧化物酶（LPO）是哺乳动物乳中一种具有广谱抗菌活性的必需蛋白质。它使婴儿对各种致病性感染有免疫力。一些体外研究表明，药物化合物（包括常用抗生素，如氨苄西林和庆大霉素）和分子（如泼尼松龙、去甲肾上腺素等）抑制了LPO的活性。向哺乳期母亲处方此类药物可能对婴儿的健康产生不利影响。本研究旨在阐明氨苄西林、庆大霉素、阿莫西林、泼尼松龙和去甲肾上腺素对LPO抑制机制的结构方面。
      材料和方法：
      利用同系物模型建立了骆驼LPO（cLPO）的三维结构，并将其用于硅化实验研究。进行了薛定谔诱导的配合对接和结合亲和力估计实验。cLPO和配体是用Schrodinger套件中的蛋白质制备向导和Ligprep模块制备的。用广义Born和比表面积（MMGB-SA）模型估计结合亲和力的质数分子力学。
      主要成果：
      五种药物配体与cLPO形成了三到五种氢键相互作用。cLPO的氨基酸Arg-231、Asp-232、Ser-370、Arg-371和Glu-374是这些相互作用的关键。庆大霉素的结合亲和力最高，去甲肾上腺素的结合亲和力最低。
      意义：
      这项研究表明，这五种药物分子具有潜在的抑制LPO活性的能力。此外，cLPO与人类LPO序列的高度相似性使这些结论对人类健康尤其是新生儿的健康具有重要意义。

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.

        https://www.sciencedirect.com/science/article/abs/pii/S0024320518303680?via%3Dihub