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The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity.

ABSTRACT: We found a heterozygous C2857T mutation (R953C) in polymerase gamma (Pol-?) in an HIV-infected patient with mitochondrial toxicity. The R953C Pol-? 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.

SUBMITTER: Li M

PROVIDER: S-EPMC4997837 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

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The DNA Polymerase Gamma R953C Mutant Is Associated with Antiretroviral Therapy-Induced Mitochondrial Toxicity.

Li Min M Mislak Andrea C AC Foli Yram Y Agbosu Esinam E Bose Vivek V Bhandari Shreya S Szymanski Michal R MR Shumate Christie K CK Yin Y Whitney YW Anderson Karen S KS Paintsil Elijah E

Antimicrobial agents and chemotherapy 20160822 9

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 t ...[more]

PMID: 27381400

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