鱼源β-防御素的生物信息学分析  

Bioinformatics Analysis of Fish-Derivedβ-Defensin

作　　者：仇梓颖 马运琪 Qiu Zi-ying;Ma Yun-qi(School of Pharmacy Binzhou Medical University,Yantai Shandong 264003)

机构地区：[1]滨州医学院药学院,山东烟台264003

出　　处：《国外医药（抗生素分册）》2024年第2期136-144,I0001,共10页World Notes on Antibiotics

基　　金：滨州医学院科研启动基金(BY2021KYQD02)。

摘　　要：鱼源β-防御素是抗菌肽家族的重要成员,具有广谱抗菌、不损伤真核细胞、不易产生耐药性等特点,可应用于渔业养殖和临床医学等方面,但目前面临着提取工艺复杂、含量较低、提取所用蛋白酶需求量大及以生产成本高等问题。因此分析其理化性质、结构和杀菌功能,对构造便捷和低廉的衍生肽具有重要的意义。本研究结合生物信息学软件和工具预测分析其理化性质、二级结构、磷酸化和糖基化位点、疏水性、细胞内定位和信号肽。结果提示鱼源β-防御素均为疏水性阳离子型抗菌肽。β-防御素抗菌肽通过C端亲水作用与细菌膜结合,引导N端氨基酸的疏水作用插入膜磷酸二酯键中改变细胞膜的通透性使细菌生物膜破裂而死亡,其中AJA33388.1(红牙鳞鲀)破膜杀菌能力最强。经检测发现β-防御素耐热性,稳定性相对较好,尤其是ACO88907.1(鳜鱼)和QNV47918.1(条石鲷)具有极高耐热性,可将其应用于杀菌以外的多方面领域。其二级结构以α螺旋为主,具有一定的刚性结构,且均具有3~4个磷酸化位点,分布于细胞外,具有19~20个氨基酸的信号肽序列,指导其在胞外蛋白产物的分泌等。通过预测分析结构,可为β-防御素的深入研究和应用以及多领域的抗菌肽衍生物设计提供思路。Fish-derivedβ-defensin is an important member of the antimicrobial peptide family.It has the characteristics of broad-spectrum antibacterial,does not damage eukaryotic cells,and is not easy to express drug resistance.It can be applied to fishery breeding,human clinical and other aspects.Nevertheless,it now faces issues with a difficult extraction procedure,poor yield,high manufacturing costs,and a high demand for the proteases needed for the extraction.Thus,it is crucial to examine its physicochemical characteristics,structure,and bactericidal action as well as to create practical and affordable derived peptides.In this study,the physicochemical properties,secondary structure,phosphorylation and glycosylation sites,hydrophobicity,intracellular localization and signal peptide were predicted and analyzed by bioinformatics tools.The results showed that fishβ-defensins were hydrophobic cationic antimicrobial peptides.Theβ-defensin antimicrobial peptide binds to the bacterial membrane through the C-terminal hydrophilic effect,and guides the hydrophobic action of the N-terminal amino acid to insert into the membrane lipid bond to change the permeability of the cell membrane and cause the bacterial biofilm to rupture and die.It was found thatβ-defensins were heat-resistant and relatively stable,especially ACO88907.1(mandarin fish)and QNV47918.1(striped sea bream)had extremely high heat resistance,which could be applied to many fields other than sterilization.Alpha helices make up the majority of its secondary structure,which has a rather rigid shape.All of its phosphorylation sites,which are dispersed outside of cells,have a signal peptide sequence consisting of 19-20 amino acids that directs the secretion of protein products into an extracellular region.By predicting and analyzing the structure,it can provide ideas for the in-depth study and application ofβ-defensins and antimicrobial peptide derivatives designs in many fields.

关 键 词：Β-防御素 生物信息学 理化性质 二级结构 

分 类 号：R978[医药卫生—药品]