The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity
We found a heterozygous C2857T mutation (R953C) in polymerase gamma (Pol-γ) in an HIV-infected patient with mitochondrial toxicity. The R953C Pol-γ mutant binding affinity for dCTP is 8-fold less than that of the wild type. The R953C mutant shows a 4-fold decrease in discrimination of analog nucleot...
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Published in | Antimicrobial agents and chemotherapy Vol. 60; no. 9; pp. 5608 - 5611 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Microbiology
01.09.2016
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Subjects | |
Online Access | Get full text |
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Summary: | We found a heterozygous C2857T mutation (R953C) in polymerase gamma (Pol-γ) in an HIV-infected patient with mitochondrial toxicity. The R953C Pol-γ mutant binding affinity for dCTP is 8-fold less than that of the wild type. The R953C mutant shows a 4-fold decrease in discrimination of analog nucleotides relative to the wild type. R953 is located on the "O-helix" that forms the substrate deoxynucleoside triphosphate (dNTP) binding site; the interactions of R953 with E1056 and Y986 may stabilize the O-helix and affect polymerase activity. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 M.L. and A.C.M. contributed equally to this article. Citation Li M, Mislak AC, Foli Y, Agbosu E, Bose V, Bhandari S, Szymanski MR, Shumate CK, Yin YW, Anderson KS, Paintsil E. 2016. The DNA polymerase gamma R953C mutant is associated with antiretroviral therapy-induced mitochondrial toxicity. Antimicrob Agents Chemother 60:5608–5611. doi:10.1128/AAC.00976-16. |
ISSN: | 0066-4804 1098-6596 |
DOI: | 10.1128/AAC.00976-16 |