{"title":"群体感应相关细菌吩嗪是人类α1-酸性糖蛋白的潜在配体","authors":"Ferenc Zsila","doi":"10.1002/jmr.3027","DOIUrl":null,"url":null,"abstract":"<p>α<sub>1</sub>-Acid glycoprotein (AGP) is a prominent acute phase component of blood plasma and extravascular fluids. As a member of the immunocalins, AGP exerts protective effects against Gram-negative bacterial infections but the underlying molecular mechanisms still need to be elucidated. Notably, the chemical structures of phenothiazine, phenoxazine and acridine type ligands of AGP are similar to those of phenazine compounds excreted by the opportunistic human pathogen <i>Pseudomonas aeruginosa</i> and related bacterial species. These molecules, like pyocyanin, act as quorum sensing-associated virulence factors and are important contributors to bacterial biofilm formation and host colonisation. Molecular docking simulations revealed that these agents fit into the multi-lobed cavity of AGP. The binding site is decorated by several aromatic residues which seem to be essential for molecular recognition of the ligands allowing multifold π–π and CH–π interactions. The estimated affinity constants (~10<sup>5</sup> M<sup>−1</sup>) predict that these secondary metabolites could be trapped inside the β-barrel of AGP which in turn could reduce their cytotoxic effects and disrupt the microbial QS network, facilitating the eradication of bacterial infections.</p>","PeriodicalId":16531,"journal":{"name":"Journal of Molecular Recognition","volume":"36 7","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Quorum sensing-associated bacterial phenazines are potential ligands of human α1-acid glycoprotein\",\"authors\":\"Ferenc Zsila\",\"doi\":\"10.1002/jmr.3027\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>α<sub>1</sub>-Acid glycoprotein (AGP) is a prominent acute phase component of blood plasma and extravascular fluids. As a member of the immunocalins, AGP exerts protective effects against Gram-negative bacterial infections but the underlying molecular mechanisms still need to be elucidated. Notably, the chemical structures of phenothiazine, phenoxazine and acridine type ligands of AGP are similar to those of phenazine compounds excreted by the opportunistic human pathogen <i>Pseudomonas aeruginosa</i> and related bacterial species. These molecules, like pyocyanin, act as quorum sensing-associated virulence factors and are important contributors to bacterial biofilm formation and host colonisation. Molecular docking simulations revealed that these agents fit into the multi-lobed cavity of AGP. The binding site is decorated by several aromatic residues which seem to be essential for molecular recognition of the ligands allowing multifold π–π and CH–π interactions. The estimated affinity constants (~10<sup>5</sup> M<sup>−1</sup>) predict that these secondary metabolites could be trapped inside the β-barrel of AGP which in turn could reduce their cytotoxic effects and disrupt the microbial QS network, facilitating the eradication of bacterial infections.</p>\",\"PeriodicalId\":16531,\"journal\":{\"name\":\"Journal of Molecular Recognition\",\"volume\":\"36 7\",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2023-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Recognition\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jmr.3027\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Recognition","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jmr.3027","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Quorum sensing-associated bacterial phenazines are potential ligands of human α1-acid glycoprotein
α1-Acid glycoprotein (AGP) is a prominent acute phase component of blood plasma and extravascular fluids. As a member of the immunocalins, AGP exerts protective effects against Gram-negative bacterial infections but the underlying molecular mechanisms still need to be elucidated. Notably, the chemical structures of phenothiazine, phenoxazine and acridine type ligands of AGP are similar to those of phenazine compounds excreted by the opportunistic human pathogen Pseudomonas aeruginosa and related bacterial species. These molecules, like pyocyanin, act as quorum sensing-associated virulence factors and are important contributors to bacterial biofilm formation and host colonisation. Molecular docking simulations revealed that these agents fit into the multi-lobed cavity of AGP. The binding site is decorated by several aromatic residues which seem to be essential for molecular recognition of the ligands allowing multifold π–π and CH–π interactions. The estimated affinity constants (~105 M−1) predict that these secondary metabolites could be trapped inside the β-barrel of AGP which in turn could reduce their cytotoxic effects and disrupt the microbial QS network, facilitating the eradication of bacterial infections.
期刊介绍:
Journal of Molecular Recognition (JMR) publishes original research papers and reviews describing substantial advances in our understanding of molecular recognition phenomena in life sciences, covering all aspects from biochemistry, molecular biology, medicine, and biophysics. The research may employ experimental, theoretical and/or computational approaches.
The focus of the journal is on recognition phenomena involving biomolecules and their biological / biochemical partners rather than on the recognition of metal ions or inorganic compounds. Molecular recognition involves non-covalent specific interactions between two or more biological molecules, molecular aggregates, cellular modules or organelles, as exemplified by receptor-ligand, antigen-antibody, nucleic acid-protein, sugar-lectin, to mention just a few of the possible interactions. The journal invites manuscripts that aim to achieve a complete description of molecular recognition mechanisms between well-characterized biomolecules in terms of structure, dynamics and biological activity. Such studies may help the future development of new drugs and vaccines, although the experimental testing of new drugs and vaccines falls outside the scope of the journal. Manuscripts that describe the application of standard approaches and techniques to design or model new molecular entities or to describe interactions between biomolecules, but do not provide new insights into molecular recognition processes will not be considered. Similarly, manuscripts involving biomolecules uncharacterized at the sequence level (e.g. calf thymus DNA) will not be considered.