iScience (Jan 2021)
Structural insights into the inhibition of bacterial RecA by naphthalene polysulfonated compounds
- Ziyuan Zhou,
- Qing Pan,
- Xinchen Lv,
- Jing Yuan,
- Yang Zhang,
- Ming-Xia Zhang,
- Ming Ke,
- Xiao-Mei Mo,
- Yong-Li Xie,
- Yingxia Liu,
- Ting Chen,
- Mingchan Liang,
- Feng Yin,
- Lei Liu,
- Yiqing Zhou,
- Kun Qiao,
- Rui Liu,
- Zigang Li,
- Nai-Kei Wong
Affiliations
- Ziyuan Zhou
- Department of Pharmacology, Shantou University Medical College, Shantou 515041, China; National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
- Qing Pan
- Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences and Oceanology, Shenzhen University, Shenzhen 518055, China
- Xinchen Lv
- Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes, Institute of Plant and Food Science, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China; National Key Laboratory of Plant Molecular Genetics & Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 201602, China
- Jing Yuan
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
- Yang Zhang
- CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China
- Ming-Xia Zhang
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
- Ming Ke
- BGI-Shenzhen, Shenzhen 518083, China
- Xiao-Mei Mo
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
- Yong-Li Xie
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
- Yingxia Liu
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
- Ting Chen
- CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China
- Mingchan Liang
- Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518055, China
- Feng Yin
- Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518055, China; State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China
- Lei Liu
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
- Yiqing Zhou
- School of Biotechnology and Food Engineering, Changshu Institute of Technology, Changshu, Jiangsu 215500, China
- Kun Qiao
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China
- Rui Liu
- Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes, Institute of Plant and Food Science, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China; National Key Laboratory of Plant Molecular Genetics & Shanghai Center for Plant Stress Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 201602, China; Corresponding author
- Zigang Li
- Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518055, China; State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China; Corresponding author
- Nai-Kei Wong
- Department of Pharmacology, Shantou University Medical College, Shantou 515041, China; National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen 518112, China; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 1
p. 101952
Abstract
Summary: As a promising target for alternative antimicrobials, bacterial recombinase A (RecA) protein has attracted much attention for its roles in antibiotic-driven SOS response and mutagenesis. Naphthalene polysulfonated compounds (NPS) such as suramin have previously been explored as antibiotic adjuvants targeting RecA, although the underlying structural bases for RecA-ligand interactions remain obscure. Based on our in silico predictions and documented activity of NPS in vitro, we conclude that the analyzed NPS likely interact with Tyr103 (Y103) and other key residues in the ATPase activity center (pocket A). For validation, we generated recombinant RecA proteins (wild-type versus Y103 mutant) to determine the binding affinities for RecA protein interactions with suramin and underexamined NPS in isothermal titration calorimetry. The corresponding dissociation constants (Kd) ranged from 11.5 to 18.8 μM, and Y103 was experimentally shown to be critical to RecA-NPS interactions.
