Elucidating the Kinetic Mechanism of DNA Polymerization Catalyzed bySulfolobus solfataricusP2 DNA Polymerase B1

Biochemistry ◽  
2009 ◽  
Vol 48 (31) ◽  
pp. 7502-7511 ◽  
Author(s):  
Jessica A. Brown ◽  
Zucai Suo
Biochemistry ◽  
2013 ◽  
Vol 52 (40) ◽  
pp. 7041-7049 ◽  
Author(s):  
Walter J. Zahurancik ◽  
Seth J. Klein ◽  
Zucai Suo

Biochemistry ◽  
2011 ◽  
Vol 50 (45) ◽  
pp. 9865-9875 ◽  
Author(s):  
Paul B. Balbo ◽  
Eric Chun-Wei Wang ◽  
Ming-Daw Tsai

1996 ◽  
Vol 264 (3) ◽  
pp. 440-452 ◽  
Author(s):  
Mark C. Young ◽  
Steven E. Weitzel ◽  
Peter H. von Hippel

2013 ◽  
Vol 135 (24) ◽  
pp. 9149-9155 ◽  
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Kate R. Lieberman ◽  
Joseph M. Dahl ◽  
Ai H. Mai ◽  
Ashley Cox ◽  
Mark Akeson ◽  
...  

2011 ◽  
Vol 56 (1) ◽  
pp. 197-201 ◽  
Author(s):  
Sunwen Chou ◽  
Gail Marousek ◽  
Terry L. Bowlin

ABSTRACTHuman cytomegalovirus (CMV) UL54 DNA polymerase (pol) mutants with known patterns of resistance to current antivirals ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV) were tested for cyclopropavir (CPV) susceptibility by a standardized reporter-based yield reduction assay. Exonuclease and A987G (region V) mutations at codons commonly associated with dual GCV-CDV resistance in clinical isolates paradoxically conferred increased CPV susceptibility. Various polymerase catalytic region mutations conferring FOS resistance with variable low-grade GCV and CDV cross-resistance also conferred CPV resistance, with 50% effective concentration (EC50) increases of 3- to 13-fold. CPV EC50values against severalpolmutants were increased about 2-fold by adding UL97 mutation C592G. Propagation of a CMV exonuclease mutant under CPV selected forpolmutations less often than UL97 mutations. In 21 experiments, one instance each of mutations E756D and M844V, which were shown individually to confer 3- to 4-fold increases in CPV EC50, was detected. Unlike GCV and CDV, exonuclease mutations are not a preferred mechanism of CPV resistance, but mutations in and nearpolregion III may confer CPV resistance by affecting its recognition as an incoming base for DNA polymerization.


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