DNA Polymerase β:  Structure−Fidelity Relationship from Pre-Steady-State Kinetic Analyses of All Possible Correct and Incorrect Base Pairs for Wild Type and R283A Mutant†

Biochemistry ◽  
1997 ◽  
Vol 36 (5) ◽  
pp. 1100-1107 ◽  
Author(s):  
Jinwoo Ahn ◽  
Brian G. Werneburg ◽  
Ming-Daw Tsai
Keyword(s):  
Steady State ◽  
Dna Polymerase ◽  
Wild Type ◽  
Dna Polymerase Β ◽  
Base Pairs ◽  
Steady State Kinetic ◽  
State Kinetic

DNA Polymerase β:  Pre-Steady-State Kinetic Analysis and Roles of Arginine-283 in Catalysis and Fidelity†

Biochemistry ◽  
1996 ◽  
Vol 35 (22) ◽  
pp. 7041-7050 ◽  
Author(s):  
Brian G. Werneburg ◽  
Jinwoo Ahn ◽  
Xuejun Zhong ◽  
Robert J. Hondal ◽  
Vadim S. Kraynov ◽  
...  
Keyword(s):  
Steady State ◽  
Kinetic Analysis ◽  
Dna Polymerase ◽  
Dna Polymerase Β ◽  
Steady State Kinetic ◽  
State Kinetic

DNA Polymerase β Fidelity:  Halomethylene-Modified Leaving Groups in Pre-Steady-State Kinetic Analysis Reveal Differences at the Chemical Transition State†

Biochemistry ◽  
2008 ◽  
Vol 47 (3) ◽  
pp. 870-879 ◽  
Author(s):  
Christopher A. Sucato ◽  
Thomas G. Upton ◽  
Boris A. Kashemirov ◽  
Jorge Osuna ◽  
Keriann Oertell ◽  
...  
Keyword(s):  
Steady State ◽  
Transition State ◽  
Kinetic Analysis ◽  
Dna Polymerase ◽  
Dna Polymerase Β ◽  
Steady State Kinetic ◽  
Leaving Groups ◽  
State Kinetic

scholarly journals Variation in the Steady State Kinetic Parameters of Wild Type and Mutant T5 5′-3′-Exonuclease With pH

1999 ◽  
Vol 274 (25) ◽  
pp. 17711-17717 ◽  
Author(s):  
Timothy J. Pickering ◽  
Scott Garforth ◽  
Jon R. Sayers ◽  
Jane A. Grasby
Keyword(s):  
Steady State ◽  
Kinetic Parameters ◽  
Wild Type ◽  
Steady State Kinetic ◽  
State Kinetic

Pre-Steady-State Kinetic Studies of the Fidelity of Human DNA Polymerase μ†

Biochemistry ◽  
2004 ◽  
Vol 43 (43) ◽  
pp. 13827-13838 ◽  
Author(s):  
Michelle P. Roettger ◽  
Kevin A. Fiala ◽  
Susmitha Sompalli ◽  
Yuxia Dong ◽  
Zucai Suo
Keyword(s):  
Steady State ◽  
Dna Polymerase ◽  
Kinetic Studies ◽  
Human Dna ◽  
Steady State Kinetic ◽  
State Kinetic

scholarly journals Pre-Steady-State Kinetic Analysis of the Incorporation of Anti-HIV Nucleotide Analogs Catalyzed by Human X- and Y-Family DNA Polymerases

2010 ◽  
Vol 55 (1) ◽  
pp. 276-283 ◽  
Author(s):  
Jessica A. Brown ◽  
Lindsey R. Pack ◽  
Jason D. Fowler ◽  
Zucai Suo
Keyword(s):  
Mitochondrial Dna ◽  
Steady State ◽  
Substrate Specificity ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Steady State Kinetic ◽  
Y Family ◽  
State Kinetic

ABSTRACTNucleoside reverse transcriptase inhibitors (NRTIs) are an important class of antiviral drugs used to manage infections by human immunodeficiency virus, which causes AIDS. Unfortunately, these drugs cause unwanted side effects, and the molecular basis of NRTI toxicity is not fully understood. Putative routes of NRTI toxicity include the inhibition of human nuclear and mitochondrial DNA polymerases. A strong correlation between mitochondrial toxicity and NRTI incorporation catalyzed by human mitochondrial DNA polymerase has been established bothin vitroandin vivo. However, it remains to be determined whether NRTIs are substrates for the recently discovered human X- and Y-family DNA polymerases, which participate in DNA repair and DNA lesion bypassin vivo. Using pre-steady-state kinetic techniques, we measured the substrate specificity constants for human DNA polymerases β, λ, η, ι, κ, and Rev1 incorporating the active, 5′-phosphorylated forms of tenofovir, lamivudine, emtricitabine, and zidovudine. For the six enzymes, all of the drug analogs were incorporated less efficiently (40- to >110,000-fold) than the corresponding natural nucleotides, usually due to a weaker binding affinity and a slower rate of incorporation for the incoming nucleotide analog. In general, the 5′-triphosphate forms of lamivudine and zidovudine were better substrates than emtricitabine and tenofovir for the six human enzymes, although the substrate specificity profile depended on the DNA polymerase. Our kinetic results suggest NRTI insertion catalyzed by human X- and Y-family DNA polymerases is a potential mechanism of NRTI drug toxicity, and we have established a structure-function relationship for designing improved NRTIs.

Steady-State Kinetic Characterization of RB69 DNA Polymerase Mutants Τhat Affect dNTP Incorporation†

Biochemistry ◽  
1999 ◽  
Vol 38 (25) ◽  
pp. 8094-8101 ◽  
Author(s):  
Guangwei Yang ◽  
T.-C. Lin ◽  
J. Karam ◽  
W. H. Konigsberg
Keyword(s):  
Steady State ◽  
Dna Polymerase ◽  
Kinetic Characterization ◽  
Steady State Kinetic ◽  
Polymerase Mutants ◽  
State Kinetic
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