Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/74994
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Type: | Journal article |
Title: | Dual inhibition of DNA polymerase PolC and protein tyrosine phosphatase CpsB uncovers a novel antibiotic target |
Author: | Standish, A. Salim, A. Capon, R. Morona, R. |
Citation: | Biochemical and Biophysical Research Communications, 2013; 430(1):167-172 |
Publisher: | Academic Press Inc |
Issue Date: | 2013 |
ISSN: | 0006-291X 1090-2104 |
Statement of Responsibility: | Alistair J. Standish, Angela A. Salim, Robert J. Capon, Renato Morona |
Abstract: | Increasing antibiotic resistance is making the identification of novel antimicrobial targets critical. Recently, we discovered an inhibitor of protein tyrosine phosphatase CpsB, fascioquinol E (FQE), which unexpectedly inhibited the growth of Gram-positive pathogens. CpsB is a member of the polymerase and histidinol phosphate phosphatase (PHP) domain family. Another member of this family found in a variety of Gram-positive pathogens is DNA polymerase PolC. We purified the PHP domain from PolC (PolC(PHP)), and showed that this competes away FQE inhibition of CpsB phosphatase activity. Furthermore, we showed that this domain hydrolyses the 5'-p-nitrophenyl ester of thymidine-5'-monophosphate (pNP-TMP), which has been used as a measure of exonuclease activity. Finally, we showed that FQE not only inhibits the phosphatase activity of CpsB, but also ability of PolC(PHP) to catalyse the hydrolysis of pNP-TMP. This suggests that PolC may be the essential target of FQE, and that the PHP domain may represent an as yet untapped target for the development of novel antibiotics. |
Keywords: | Bacteria Antibiotic DNA polymerase Exonuclease Polymerase and histidinol phosphate domain |
Rights: | © 2012 Elsevier Inc. All rights reserved. |
DOI: | 10.1016/j.bbrc.2012.11.049 |
Published version: | http://dx.doi.org/10.1016/j.bbrc.2012.11.049 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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hdl_74994.pdf | Accepted version | 484.23 kB | Adobe PDF | View/Open |
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