Computational elucidation of the binding mechanisms of curcumin analogues as bacterial RecA inhibitors

Zhou, Zi-Yuan1,2; Yuan, Jing1; Pan, Qing3; Mo, Xiao-Mei1; Xie, Yong-Li1; Yin, Feng2; Li, Zigang2; Wong, Nai-Kei1

2019-06-24

10.1039/c9ra00064j

RSC Advances   影响因子和分区

2046-2069

Antimicrobial resistance (AMR) presents as a serious threat to global public health, which urgently demands action to develop alternative antimicrobial strategies with minimized selective pressure. The bacterial SOS response regulator RecA has emerged as a promising target in the exploration of new classes of antibiotic adjuvants, as RecA has been implicated in bacterial mutagenesis and thus AMR development through its critical roles in error-prone DNA repair. The natural product curcumin has been reported to be an effective RecA inhibitor in several Gram-negative bacteria, but details on the underlying mechanisms are wanting. In order to bridge the gap in how curcumin operates as a RecA inhibitor, we used computational approaches to model interactions between RecA protein and curcumin analogues. We first identified potential binding sites on E. coli RecA protein and classified them into four major binding pockets based on biological literature and computational findings from multiple in silico calculations. In docking analysis, curcumin-thalidomide hybrids were predicted to be superior binders of RecA compared with bis-(arylmethylidene)acetone curcumin analogues, which was further confirmed by MMGBSA calculations. Overall, this work provides mechanistic insights into bacterial RecA protein as a target for curcumin-like compounds and offers a theoretical basis for rational design and development of future antibiotic adjuvants.

SCI ; EI

英语

第一 ; 通讯

China Postdoctoral Science Foundation[2018M641097]

Chemistry

Chemistry, Multidisciplinary

WOS:000475455200065

ROYAL SOC CHEMISTRY

20192707139243

Acetone ; Antibiotics ; Escherichia coli ; Health risks ; Proteins

Medicine and Pharmacology:461.6 ; Health Care:461.7 ; Biochemistry:801.2 ; Organic Compounds:804.1

Web of Science

1.Southern Univ Sci & Technol, Hosp 2, Shenzhen Peoples Hosp 3, Dept Infect Dis, Shenzhen 518112, Peoples R China
2.Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Dept Chem Biol, Shenzhen 518055, Peoples R China
3.Shenzhen Univ, Coll Life Sci & Oceanol, Shenzhen Key Lab Microbial Genet Engn, Shenzhen 518055, Peoples R China

Zhou, Zi-Yuan,Yuan, Jing,Pan, Qing,et al. Computational elucidation of the binding mechanisms of curcumin analogues as bacterial RecA inhibitors[J]. RSC Advances,2019,9(34):19869-19881.

Zhou, Zi-Yuan.,Yuan, Jing.,Pan, Qing.,Mo, Xiao-Mei.,Xie, Yong-Li.,...&Wong, Nai-Kei.(2019).Computational elucidation of the binding mechanisms of curcumin analogues as bacterial RecA inhibitors.RSC Advances,9(34),19869-19881.

Zhou, Zi-Yuan,et al."Computational elucidation of the binding mechanisms of curcumin analogues as bacterial RecA inhibitors".RSC Advances 9.34(2019):19869-19881.