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Mining Novel Anti-
Nocardia Drug Targets Based on Pan-genomics and Subtractive Proteomics- Journal of Sun Yat-sen University(Medical Sciences) Vol. 44, Issue 6, Pages: 974-982(2023)
- 作者机构：
广东药科大学基础医学院/广东省生物活性药物研究重点实验室，广东 广州 510006
- 作者简介：
JIN Xiao-bao； E-mail： jinxf2001@163.com
- 基金信息：
DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0611
CLC： R3Published：20 November 2023，
Received：01 June 2023，
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黎尔彤,苏雅琳,刘文彬等.基于泛基因组学和消减蛋白质组学挖掘新型抗诺卡氏菌药物靶点[J].中山大学学报（医学科学版）,2023,44(06):974-982.
LI Er-tong,SU Ya-lin,LIU Wen-bin,et al.Mining Novel Anti-Nocardia Drug Targets Based on Pan-genomics and Subtractive Proteomics[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(06):974-982.
黎尔彤,苏雅琳,刘文彬等.基于泛基因组学和消减蛋白质组学挖掘新型抗诺卡氏菌药物靶点[J].中山大学学报（医学科学版）,2023,44(06):974-982. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0611.
LI Er-tong,SU Ya-lin,LIU Wen-bin,et al.Mining Novel Anti-Nocardia Drug Targets Based on Pan-genomics and Subtractive Proteomics[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(06):974-982. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0611.
摘要
目的
2
诺卡氏菌是一种病原体，可引起人体的机会性感染，呈全球性分布。近年来发现诺卡氏菌对常用药物已产生耐药性，因此，挖掘新抗诺卡氏菌药物靶点、开发新药物具有迫切需求。
方法
2
取GenBank数据库中31株诺卡氏菌的全基因组序列，利用BPGA进行泛基因组学分析，利用消减蛋白组学筛选药物靶点。在此基础上，同源建模预测靶点蛋白的3D结构，采用DrugBank对靶点蛋白进行潜在药物的预测，并使用分子对接技术验证药物与靶点的结合活性。
结果
2
31株诺卡氏菌的泛基因组中有1 421个核心蛋白，消减蛋白组学分析获得15个候选药物靶点蛋白。其中，OG1493蛋白的理化性质（氨基酸数目、分子量、等电点、总平均亲水性、脂肪指数和不稳定性指数Ⅱ等）最符合作为靶点蛋白的理化性质。运用DrugBank数据库筛选出Adenosine-5'-Rp-Alpha-Thio-Triphosphate、 alpha，beta-Methyleneadenosine 5'-triphosphate、 Phosphoaminophosphonic Acid-Adenylate Ester 、Radicicol、2-Hydroxyestradiol、p-Coumaric acid、Ethylmercurithiosalicylic acid等7个化合物可能会针对该靶点蛋白发挥抗诺卡氏菌作用，分子对接结果显示靶点与化合物结合力良好。经实验验证发现根赤壳霉素可能是针对该靶点的抗诺卡氏菌药物。
结论
2
泛基因组学和消减蛋白质组学可应用于挖掘新型抗诺卡氏菌药物靶点 。
Abstract
Objective
2
Nocardia
is an apathogen that causes opportunistic infections in humans and has a global distribution. In recent years， resistance of
Nocardia
to commonly used drugs have been observed， highlighting the urgent need for the identification of new drug targets and the development of novel antimicrobial agents against
Nocardia.
Methods
2
Thirty-one complete genome sequences of
Nocardia
strains were retrieved from the GenBank database. Pan-genomic analysis was performed using BPGA， and drug target candidates were screened using subtractive proteomics. Homology modeling was employed to predict the 3D structures of target proteins， and potential drugs targeting these proteins were predicted using DrugBank. Molecular docking techniques were utilized to validate the binding activity between the drugs and target proteins.
Results
2
The pan-genomic analysis of the 31
Nocardia
strains revealed 1 421 core proteins. Fifteen candidate drug target proteins were identified through subtractive proteomics analysis. Among them， the physicochemical properties of the OG1493 protein （such as amino acid count， molecular weight， isoelectric point， grand average of hydropathicity， fat index，and instability index Ⅱ） were found to be most suitable for a drug target protein. Using the DrugBank database， seven compounds， namely Adenosine-5'-Rp-Alpha-Thio-Triphosphate， alpha，beta-Methyleneadenosine 5'-triphosphate， Phosphoaminophosphonic Acid-Adenylate Ester ，Radicicol，2-Hydroxyestradiol， p-Coumaric acid， and Ethylmercurithiosalicylic acid were identified as potential compounds capable of exerting anti-
Nocardia
effects by targeting this protein. Molecular docking results indicated a strong binding affinity between the target protein and these compounds. The experimental result showed that that Radicicol could be a potential antibacterial drug targeting this particular protein.
Conclusion
2
Pan-genomic analysis and subtractive proteomics are valuable approaches for mining novel anti-
Nocardia
drug targets.
关键词
诺卡氏菌泛基因组学消减蛋白质组学核心基因药物靶点
Keywords
Nocardiapan-genomicssubtractive proteomicscore genedrug target
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