Dual inhibition of DNA polymerase PolC and protein tyrosine phosphatase CpsB uncovers a novel antibiotic target

Standish, Alistair J., Salim, Angela A., Capon, Robert J. and Morona, Renato (2013) Dual inhibition of DNA polymerase PolC and protein tyrosine phosphatase CpsB uncovers a novel antibiotic target. Biochemical and Biophysical Research Communications, 430 1: 167-172. doi:10.1016/j.bbrc.2012.11.049


Author Standish, Alistair J.
Salim, Angela A.
Capon, Robert J.
Morona, Renato
Title Dual inhibition of DNA polymerase PolC and protein tyrosine phosphatase CpsB uncovers a novel antibiotic target
Journal name Biochemical and Biophysical Research Communications   Check publisher's open access policy
ISSN 0006-291X
1090-2104
Publication date 2013-01-04
Year available 2012
Sub-type Article (original research)
DOI 10.1016/j.bbrc.2012.11.049
Volume 430
Issue 1
Start page 167
End page 172
Total pages 6
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Collection year 2013
Language eng
Formatted 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 (PolCPHP), 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 PolCPHP 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
Keyword Antibiotic
Bacteria
DNA polymerase
Exonuclease
Polymerase and histidinol phosphate domain
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online: 27 November 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Fri, 18 Jan 2013, 10:18:35 EST by Susan Allen on behalf of Institute for Molecular Bioscience