Structural insights into the inhibition of bacterial RecA by naphthalene polysulfonated compounds

Zhou, Ziyuan1,2; Pan, Qing5; Lv, Xinchen7,8,9; Yuan, Jing2; Zhang, Yang6; Zhang, Ming-Xia2; Ke, Ming11; Mo, Xiao-Mei2; Xie, Yong-Li2; Liu, Yingxia2; Chen, Ting6; Liang, Mingchan3; Yin, Feng3,4; Liu, Lei2; Zhou, Yiqing10; Qiao, Kun2; Liu, Rui7,8,9; Li, Zigang3,4; Wong, Nai-Kei1,2

2021-01-22

10.1016/j.isci.2020.101952

ISCIENCE   影响因子和分区

2589-0042

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 (K-d) ranged from 11.5 to 18.8 mu M, and Y103 was experimentally shown to be critical to RecA-NPS interactions.

SCI

英语

通讯

Sanming Project of Medicine in Shenzhen["SZSM201812058","SZSM201512005"] ; Foundation for Basic and Applied Research of Guangdong Province[2019A1515110489] ; High-Level Professional Program of Shenzhen[20191226897H] ; Shenlong High-level talent program[2020011056C] ; Natural Science Foundation of Jiangsu Province of China[BK20191477] ; Natural Science Foundation of the Higher Education Institutions of Jiangsu Province of China[19KJB150001] ; Natural Science Foundation of China[32073002,21778009,21977010,81701818,51803006] ; Shenzhen Science and Technology Innovation Committee["JCYJ20170817172023838","JCYJ20180508152213145","JCYJ20180507181527112"]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000612996900070

CELL PRESS

Web of Science

1.Shantou Univ, Dept Pharmacol, Med Coll, Shantou 515041, Peoples R China
2.Southern Univ Sci & Technol, Natl Clin Res Ctr Infect Dis, Shenzhen Peoples Hosp 3, Hosp 2, Shenzhen 518112, Peoples R China
3.Shenzhen Bay Lab, Pingshan Translat Med Ctr, Shenzhen 518055, Peoples R China
4.Peking Univ, State Key Lab Chem Oncogen, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China
5.Shenzhen Univ, Shenzhen Key Lab Microbial Genet Engn, Coll Life Sci & Oceanol, Shenzhen 518055, Peoples R China
6.Chinese Acad Sci, CAS Key Lab Trop Marine Bioresources & Ecol, Guangdong Prov Key Lab Appl Marine Biol, South China Sea Inst Oceanol, 164 West Xingang Rd, Guangzhou 510301, Peoples R China
7.Southern Univ Sci & Technol, Sch Life Sci, Inst Plant & Food Sdence, Key Lab Mol Design Plant Cell Factory,Guangdong H, Shenzhen 518055, Peoples R China
8.Chinese Acad Sci, Natl Key Lab Plant Mol Genet, CAS Ctr Excellence Mol Plant Sci, Shanghai 201602, Peoples R China
9.Chinese Acad Sci, Shanghai Ctr Plant Stress Biol, Shanghai 201602, Peoples R China
10.Changshu Inst Technol, Sch Biotechnol & Food Engn, Changshu 215500, Jiangsu, Peoples R China
11.BGI Shenzhen, Shenzhen 518083, Peoples R China

Zhou, Ziyuan,Pan, Qing,Lv, Xinchen,et al. Structural insights into the inhibition of bacterial RecA by naphthalene polysulfonated compounds[J]. ISCIENCE,2021,24(1).

Zhou, Ziyuan.,Pan, Qing.,Lv, Xinchen.,Yuan, Jing.,Zhang, Yang.,...&Wong, Nai-Kei.(2021).Structural insights into the inhibition of bacterial RecA by naphthalene polysulfonated compounds.ISCIENCE,24(1).

Zhou, Ziyuan,et al."Structural insights into the inhibition of bacterial RecA by naphthalene polysulfonated compounds".ISCIENCE 24.1(2021).