Sujata Adhana, Ravi Jain, Sibasis Sahoo, Sheetal Thakur, Archna Pandey, Avneesh Mittal, Bishwajit Kundu, Uma Chaudhry
{"title":"Superbug Neisseria gonorrhoeae Infections: The Role of the Moonlighting Protein Glutamate Racemase in Treatment and Prevention.","authors":"Sujata Adhana, Ravi Jain, Sibasis Sahoo, Sheetal Thakur, Archna Pandey, Avneesh Mittal, Bishwajit Kundu, Uma Chaudhry","doi":"10.2174/0115680266365593250415101135","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Neisseria gonorrhoeae is a notorious superbug responsible for causing 'Gonorrhoea' in humans. Recently, it has been classified as a high-priority pathogen by the World Health Organization due to its increasing resistance to available antibiotics. A multi-prolonged approach is needed to combat the growing problem of drug resistance caused by N. gonorrhoeae. This study evaluates Glutamate Racemase (GR), a moonlighting protein of N. gonorrhoeae (Ng- GR), as a novel therapeutic target with potential for both inhibitor design and peptide vaccine development. Ng-GR plays a crucial role in the peptidoglycan biosynthetic pathway and is highly conserved across bacterial species. Additionally, this protein moonlights to perform a secondary function by binding to DNA gyrase in various organisms.</p><p><strong>Method: </strong>Homology modeling, molecular docking, and molecular dynamics simulations were used to design inhibitors targeting the moonlight function of Ng-GR. The immunogenicity of this protein was assessed using ABCPred-2.0, BepiPred-2.0, and ProPred software.</p><p><strong>Results: </strong>Bisleucocurine A was found to bind at the ectopic site of Ng-GR, disrupting its crucial moonlight function and interfering with the interaction between Ng-GR and N. gonorroheae DNA Gyrase (Ng-gyrase). Interestingly, residues important for its moonlight function were also identified as key immunogenic sites using ABCPred-2.0, BepiPred-2.0, and ProPred software, enhancing the potential of this protein as a vaccine candidate.</p><p><strong>Conclusion: </strong>The GR enzyme's moonlight function is highlighted as a promising novel target for therapeutic intervention and vaccine development in N. gonorrohoeae.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current topics in medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115680266365593250415101135","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Neisseria gonorrhoeae is a notorious superbug responsible for causing 'Gonorrhoea' in humans. Recently, it has been classified as a high-priority pathogen by the World Health Organization due to its increasing resistance to available antibiotics. A multi-prolonged approach is needed to combat the growing problem of drug resistance caused by N. gonorrhoeae. This study evaluates Glutamate Racemase (GR), a moonlighting protein of N. gonorrhoeae (Ng- GR), as a novel therapeutic target with potential for both inhibitor design and peptide vaccine development. Ng-GR plays a crucial role in the peptidoglycan biosynthetic pathway and is highly conserved across bacterial species. Additionally, this protein moonlights to perform a secondary function by binding to DNA gyrase in various organisms.
Method: Homology modeling, molecular docking, and molecular dynamics simulations were used to design inhibitors targeting the moonlight function of Ng-GR. The immunogenicity of this protein was assessed using ABCPred-2.0, BepiPred-2.0, and ProPred software.
Results: Bisleucocurine A was found to bind at the ectopic site of Ng-GR, disrupting its crucial moonlight function and interfering with the interaction between Ng-GR and N. gonorroheae DNA Gyrase (Ng-gyrase). Interestingly, residues important for its moonlight function were also identified as key immunogenic sites using ABCPred-2.0, BepiPred-2.0, and ProPred software, enhancing the potential of this protein as a vaccine candidate.
Conclusion: The GR enzyme's moonlight function is highlighted as a promising novel target for therapeutic intervention and vaccine development in N. gonorrohoeae.
期刊介绍：
Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
