个人简介
Hollins University, Virginia B.A. 1977 Chemistry
Harvard University, Massachusetts Ph.D. 1982 Biological Chemistry
研究领域
Every bacterial pathogen has at least one type IA topoisomerase, providing a target for discovery of new antibiotics to combat multi-drug resistant infections, including MDR- and XDR-TB. The study of the structure and mechanism of bacterial topoisomerase I provide the basic foundation for translational application of this enzyme as a novel antibacterial target. Drug discovery research extends to anticancer drugs targeting human DNA topoisomerases. The control of DNA structure by DNA topoisomerases can affect stress response and genomic stability, with implications for bacterial pathogenesis and cancer.
近期论文
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1. Sandhaus S, Annamalai T, Welmaker G, Houghten RA, Paz C, Garcia PK, Andres A, Narula G, Rodrigues Felix C, Geden S, Netherton M, Gupta R, Rohde KH, Giulianotti MA, Tse-Dinh YC. Small Molecule Inhibitors Targeting Topoisomerase I as Novel Antituberculosis Agents. Antimicrob Agents Chemother. 2016; 60:4028-36. PMID: 27114277; PMCID: PMC4914652
2. Tiwari PB, Chapagain PP, Banda S, Darici Y, Üren A, Tse-Dinh YC. Characterization of molecular interactions between Escherichia coli RNA polymerase and topoisomerase I by molecular simulations. FEBS Lett. 2016;590:2844-51. PMID: 27448274; PMCID: PMC5014613
3. Tan K, Cao N, Cheng B, Joachimiak A, Tse-Dinh YC. Insights from the Structure of Mycobacterium tuberculosis Topoisomerase I with a novel protein fold. J Mol Biol. 2016 16;428(1):182-93. PMID: 26655023; PMCID: PMC4738035
4. Tan K, Zhou Q, Cheng B, Zhang Z, Joachimiak J, Tse-Dinh YC. Structural basis for suppression of hypernegative DNA supercoiling by E. coli topoisomerase I, Nucl Acids Res 2015; 43(22):11031-46. PMID: 26490962; PMCID: PMC4678816
5. Yang J, Annamalai T, Cheng B, Banda S, Tyagi R, Tse-Dinh YC. Antimicrobial Susceptibility and SOS-dependent Increase in Mutation Frequency are Impacted by E. coli Topoisomerase I C-terminal Point Mutation. Antimicrob Agents Chemother. 2015; 59:6195-202. PMID: 26248366; PMCID: PMC4576087
6. Tse-Dinh YC. Targeting bacterial topoisomerase I to meet the challenge of finding new antibiotics. Future Med Chem 2015; 7(4):459-71. PMID:25875873; PMCID: PMC4415981
7. Cheng B, Cao S, Vasquez V, Annamalai T, Tamayo-Castillo G, Clardy J, Tse-Dinh YC. Identification of Anziaic Acid, a Lichen depside from Hypotrachyna sp., as a New Topoisomerase Poison Inhibitor. PLOS ONE 2013, Apr 8;8(4):e60770. PMC3620467
8. Sissi C, Cheng B, Lombardo V, Tse-Dinh YC, Palumbo M. Metal ion and inter-domain interactions as functional networks in E. coli topoisomerase I. Gene. 2013 Jul 25;524(2):253-60. PMC3876943
9. Aedo S, Tse-Dinh YC. SbcCD-mediated processing of covalent gyrase-DNA complex in Escherichia coli. Antimicrob Agents Chemother. 2013 Oct;57(10):5116-9. PMC3811449
10. Lin H, Annamalai T, Bansod P, Tse-Dinh YC, Sun D. Synthesis and antibacterial evaluation of anziaic acid and analogues as topoisomerase I inhibitors. Medchemcomm. 2013 Dec 1;4(12). PMC3867937
11. Cheng B, Cao S, Vasquez V, Annamalai T, Tamayo-Castillo G, Clardy J, Tse-Dinh YC. Identification of anziaic acid, a lichen depside from Hypotrachyna sp., as a new topoisomerase poison inhibitor. PLoS One. 2013;8:e60770. PMID: 23593306; PMCID: PMC3620467
12. Narula G, Tse-Dinh YC 2012. Residues of E. coli topoisomerase I conserved for interaction with a specific cytosine base to facilitate DNA cleavage. Nucl Acids Res, 40, 9233-9243. PMC3467081
13. Aedo S, Tse-Dinh YC. Isolation and quantitation of topoisomerase complexes accumulated on E. coli chromosomal DNA. Antimicrob Agents Chemother 2012, Nov; 56(11):5458-64. PMC3486612
14. Bansal S, Singh M, Sinha D, Cheng B, Tse-Dinh YC, Tandon V. 3, 4 dimethoxyphenyl bis-benzimidazole, a novel DNA Topoisomerase Inhibitor that Preferentially Targets E. coli Topoisomerase I. J Antimicrob Chemother 2012 Dec; 67(12):2882-91
15. Narula G, Tse-Dinh YC. Residues of E. coli topoisomerase I conserved for interaction with a specific cytosine base to facilitate DNA cleavage. Nucleic Acids Res. 2012; 40:9233-43. PMID: 22833607; PMCID: PMC3467081
16. Zhang Z, Cheng B, Tse-Dinh YC. Crystal structure of a covalent intermediate in DNA cleavage and rejoining by Escherichia coli DNA topoisomerase I. Proc Natl Acad Sci USA. 2011; 108:6939-6944. PMID: 21482796; PMCID: PMC3084087
17. Narula G, Annamalai T, Aedo S, Cheng B, Sorokin E, Wong A, Tse-Dinh YC 2011. The strictly conserved Arg-321 residue in the active site of Escherichia coli topoisomerase I plays a critical role in DNA rejoining. J Biol Chem 286, 18673-18682. PMC3099684
18. Liu IF, Sutherland JH, Cheng B, Tse-Dinh YC 2011. Topoisomerase I function during Escherichia coli response to antibiotics and stress enhances cell killing from stabilization of its cleavage complex. J Antimicrob Chemother. 66, 1518-1524. PMC3112028
19. Zhang Z, Cheng B, Tse-Dinh YC 2011. Crystal structure of a covalent intermediate in DNA cleavage and rejoining by Escherichia coli DNA topoisomerase I. Proc Natl Acad Sci USA 108, 6939-6944. PMC3084087
20. Liu IF, Sutherland JH, Cheng B, Tse-Dinh YC. Topoisomerase I function during Escherichia coli response to antibiotics and stress enhances cell killing from stabilization of its cleavage complex. J Antimicrob Chemother. 2011; 66:1518-24. PMID: 21486853; PMCID: PMC3112028
21. Sutherland JH, Tse-Dinh YC 2010. Analysis of RuvABC and RecG involvement in the Escherichia coli response to the covalent topoisomerase-DNA complex. J Bacteriol 192, 4445-51. PMC2937393
22. Tse-Dinh YC 2009. Bacterial topoisomerase I as a target for discovery of antibacterial compounds. Invited peer reviewed Survey and Summary for Nucl Acids Res 37, 731-737. PMC2647297
23. Cheng B, Annamalai T, Sorokin E, Abrenica M, Aedo S, Tse-Dinh YC 2009. Asp to Asn substitution at the first position of the DxD TOPRIM motif of recombinant bacterial topoisomerase I is extremely lethal to E. coli. J Mol Biol 385, 558-67. PMC2905861
24. Sorokin, E, Cheng B, Rathi S, Aedo S, Abrenica MV, Tse-Dinh YC 2008. Inhibition of Mg2+ binding and DNA religation by bacterial topoisomerase I via introduction of additional positive charge into the active site region. Nucl Acids Res 36, 4788-96. PMC2504298
25. Cheng B, Sorokin E, Tse-Dinh YC 2008. Mutation adjacent to the active site tyrosine can enhance DNA cleavage and cell killing by the TOPRIM Gly to Ser mutant of bacterial topoisomerase I. Nucleic Acids Res. 36,1017-25. PMC2241903
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