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Mechanism of action of an imidopiperidine inhibitor of human polynucleotide kinase/phosphatase.

Abstract:

The small molecule, 2-(1-hydroxyundecyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione (A12B4C3), is a potent inhibitor of the phosphatase activity of human polynucleotide kinase/phosphatase (PNKP) in vitro. Kinetic analysis revealed that A12B4C3 acts as a noncompetitive inhibitor, and this was confirmed by fluorescence quenching, which showed that the inhibitor can form a ternary complex with PNKP and a DNA substrate, i.e. A12B4C3 does not prevent D...

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Publication status:
Published

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Publisher copy:
10.1074/jbc.m109.055764

Authors


Freschauf, GK More by this author
Mereniuk, TR More by this author
Virgen, CA More by this author
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Journal:
The Journal of biological chemistry
Volume:
285
Issue:
4
Pages:
2351-2360
Publication date:
2010-01-05
DOI:
EISSN:
1083-351X
ISSN:
0021-9258
URN:
uuid:69658b0a-5133-4518-aec4-7f60412e4767
Source identifiers:
131065
Local pid:
pubs:131065

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