title: Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A.
abstract: The intractability of bacterial resistance presents a dilemma for therapies againstStaphylococcus aureus(S. aureus) infection. Effective anti-virulence strategies are urgently needed, reflecting the proliferation of resistant strains. Inhibitors of sortase A (SrtA), enzymes that anchor virulence-related surface proteins, are regarded as promising candidates for countermeasures against bacterial infections. In the present study, the inhibitory effect of dryocrassin ABBA (ABBA) against SrtA and its molecular basis has been examined. Fluorescence resonance energy transfer (FRET) assays were used to determine the inhibitory activity of ABBA against SrtA. To identify the mechanism underlying this activity, molecular dynamics simulations and mutagenesis assays were applied, and the results revealed that the direct engagement of SrtA via ABBA through binding to V166 and V168 significantly attenuated the catalytic activity of SrtA. Taken together, these findings indicated that ABBA is a potential novel antimicrobial agent forS. aureusinfection via targeting SrtA.
authors: College of Food Science and Engineering, Jilin University, Changchun 130062, China. emerald_bing@sina.com.|College of Veterinary Medicine, Jilin University, Changchun 130062, China. emerald_bing@sina.com.
authors: Bing
authors: B
authors: Zhang
authors: College of Veterinary Medicine, Jilin University, Changchun 130062, China. wxyvip16@163.com.
authors: Xiyan
authors: X
authors: Wang
authors: College of Veterinary Medicine, Jilin University, Changchun 130062, China. wanglin1020@jlu.edu.cn.
authors: Lin
authors: L
authors: Wang
authors: College of Veterinary Medicine, Jilin University, Changchun 130062, China. 18443158548@163.com.
authors: Shuiye
authors: S
authors: Chen
authors: College of Veterinary Medicine, Jilin University, Changchun 130062, China. m15754305546@163.com.
authors: Dongxue
authors: D
authors: Shi
authors: College of Food Science and Engineering, Jilin University, Changchun 130062, China. wanghs@jlu.edu.cn.|College of Veterinary Medicine, Jilin University, Changchun 130062, China. wanghs@jlu.edu.cn.
authors: Hongsu
authors: H
authors: Wang
mesh_terms: D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D001597:Benzylidene Compounds; D001688:Biological Products / Q000494:pharmacology; D020134:Catalytic Domain / Q000187:drug effects; D003512:Cyclohexanones; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D031541:Fluorescence Resonance Energy Transfer; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016296:Mutagenesis; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D001597:Benzylidene Compounds; D001688:Biological Products; D003512:Cyclohexanones; D005419:Flavonoids; C107335:dryocrassin; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases
keywords: Staphylococcus aureus; dryocrassin; molecular simulations; sortase A