Nucleic Acids Research Advance Access originally published online on October 11, 2006
Nucleic Acids Research 2006 34(19):5650-5659; doi:10.1093/nar/gkl695
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Nucleic Acids Research, 2006, Vol. 34, No. 19 5650-5659
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nucleic Acid Enzymes |
The key DNA-binding residues in the C-terminal domain of Mycobacterium tuberculosis DNA gyrase A subunit (GyrA)
1 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences Wuhan 430071, China 2 State Key Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences Beijing 100101, China 3 State Key Laboratory of Agromicrobiology, College of Life Science and Technology, Huazhong Agricultural University Wuhan 430070, China 4 Department of Biological Chemistry, John Innes Centre Colney, Norwich NR4 7UH, UK
*To whom correspondence should be addressed. Tel: +86 010 58881508, Fax: +86 027 87199492. Email: zhangxe{at}most.cn
Received June 7, 2006. Revised September 3, 2006. Accepted September 9, 2006.
As only the type II topoisomerase is capable of introducing negative supercoiling, DNA gyrase is involved in crucial cellular processes. Although the other domains of DNA gyrase are better understood, the mechanism of DNA binding by the C-terminal domain of the DNA gyrase A subunit (GyrA-CTD) is less clear. Here, we investigated the DNA-binding sites in the GyrA-CTD of Mycobacterium tuberculosis gyrase through site-directed mutagenesis. The results show that Y577, R691 and R745 are among the key DNA-binding residues in M.tuberculosis GyrA-CTD, and that the third blade of the GyrA-CTD is the main DNA-binding region in M.tuberculosis DNA gyrase. The substitutions of Y577A, D669A, R691A, R745A and G729W led to the loss of supercoiling and relaxation activities, although they had a little effect on the drug-dependent DNA cleavage and decatenation activities, and had no effect on the ATPase activity. Taken together, these results showed that the GyrA-CTD is essential to DNA gyrase of M.tuberculosis, and promote the idea that the M.tuberculosis GyrA-CTD is a new potential target for drug design. It is the first time that the DNA-binding sites in GyrA-CTD have been identified.
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