Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1.

Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1. Research Abstract Details 

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Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1. Abstract Text:

Robyn L Maher,Linda B Bloom,Robyn L Maher,Linda B Bloom,

Human AP endonuclease 1 (APE1, REF1) functions within the base excision repair pathway by catalyzing the hydrolysis of the phosphodiester bond 5 ' to a baseless sugar (apurinic or apyrimidinic site). The AP endonuclease activity of this enzyme and two active site mutants were characterized using equilibrium binding and pre-steady-state kinetic techniques. Wild-type APE1 is a remarkably potent endonuclease and highly efficient enzyme. Incision 5 ' to AP sites is so fast that a maximal single-turnover rate could not be measured using rapid mixing/quench techniques and is at least 850 s(-1). The entire catalytic cycle is limited by a slow step that follows chemistry and generates a steady-state incision rate of about 2 s(-1). Site-directed mutation of His-309 to Asn and Asp-210 to Ala reduced the single turnover rate of incision 5 ' to AP sites by at least 5 orders of magnitude such that chemistry (or a step following DNA binding and preceding chemistry) and not a step following chemistry became rate-limiting. Our results suggest that the efficiency with which APE1 can process an AP site in vivo is limited by the rate at which it diffuses to the site and that a slow step after chemistry may prevent APE1 from leaving the site of damage before the next enzyme arrives to continue the repair process.

Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1. Publishing Authors By Initials

RL Maher,LB Bloom,RL Maher,LB Bloom,

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Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 30577-85

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 26

MONTH: 08

YEAR: 2007

Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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Grant and Affiliation Information for Pre-steady-state kinetic characterization of the AP endonuclease activity of human AP endonuclease 1.

AFFILIATION: Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida 32610-0245, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM055596

ACRONYM: GM

MEDLINETA: J Biol Chem

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