The DNA polymerase gamma R953C mutant is associated with antiretroviral therapy-induced mitochondrial toxicity

Min Li, Andrea C. Mislak, Yram Foli, Esinam Agbosu, Vivek Bose, Shreya Bhandari, Michal R. Szymanski, Christie K. Shumate, Yuhui Yin, Karen S. Anderson, Elijah Paintsil

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5608-5611
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number9
DOIs
StatePublished - Sep 1 2016

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Nucleotides
Binding Sites
HIV
Mutation
Therapeutics
2'-deoxycytidine 5'-triphosphate
triphosphoric acid
DNA polymerase gamma

ASJC Scopus subject areas

  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

The DNA polymerase gamma R953C mutant is associated with antiretroviral therapy-induced mitochondrial toxicity. / Li, Min; Mislak, Andrea C.; Foli, Yram; Agbosu, Esinam; Bose, Vivek; Bhandari, Shreya; Szymanski, Michal R.; Shumate, Christie K.; Yin, Yuhui; Anderson, Karen S.; Paintsil, Elijah.

In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 9, 01.09.2016, p. 5608-5611.

Research output: Contribution to journalArticle

Li, M, Mislak, AC, Foli, Y, Agbosu, E, Bose, V, Bhandari, S, Szymanski, MR, Shumate, CK, Yin, Y, Anderson, KS & Paintsil, E 2016, 'The DNA polymerase gamma R953C mutant is associated with antiretroviral therapy-induced mitochondrial toxicity', Antimicrobial Agents and Chemotherapy, vol. 60, no. 9, pp. 5608-5611. https://doi.org/10.1128/AAC.00976-16
Li, Min ; Mislak, Andrea C. ; Foli, Yram ; Agbosu, Esinam ; Bose, Vivek ; Bhandari, Shreya ; Szymanski, Michal R. ; Shumate, Christie K. ; Yin, Yuhui ; Anderson, Karen S. ; Paintsil, Elijah. / The DNA polymerase gamma R953C mutant is associated with antiretroviral therapy-induced mitochondrial toxicity. In: Antimicrobial Agents and Chemotherapy. 2016 ; Vol. 60, No. 9. pp. 5608-5611.
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AU - Bhandari, Shreya

AU - Szymanski, Michal R.

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