群体感应相关细菌吩嗪是人类α1-酸性糖蛋白的潜在配体

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ferenc Zsila
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引用次数: 0

摘要

α1-酸性糖蛋白(AGP)是血浆和血管外液中一种重要的急性期成分。AGP作为免疫细胞中的一员,对革兰氏阴性细菌感染具有保护作用,但其潜在的分子机制仍有待阐明。值得注意的是,AGP的吩噻嗪、吩恶嗪和吖啶型配体的化学结构与机会性人类病原体铜绿假单胞菌和相关细菌分泌的吩嗪化合物的化学结构相似。这些分子,如绿脓蛋白,作为群体感应相关毒力因子,是细菌生物膜形成和宿主定植的重要因素。分子对接模拟显示,这些试剂适合AGP的多叶腔。结合位点由几个芳香残基修饰,这些残基似乎对配体的分子识别至关重要,从而允许多重π–π和CH–π相互作用。估计的亲和常数(~105 M−1)预测,这些次级代谢产物可能被捕获在AGP的β-桶内,这反过来又可以降低其细胞毒性作用,破坏微生物QS网络,促进根除细菌感染。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Journal of Molecular Recognition
Journal of Molecular Recognition 生物-生化与分子生物学
CiteScore
4.60
自引率
3.70%
发文量
68
审稿时长
2.7 months
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.
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