| Title | DNA Polymerase-γ R953C Mutant is Associated with ART-Induced Mitochondrial Toxicity. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Li, Min, Andrea C. Mislak, Yram Foli, Esinam Agbosu, Vivek Bose, Shreya Bhandari, Michal R. Szymanski, Christie K. Shumate, Whitney Y. Yin, Karen S. Anderson, and Elijah Paintsil |
| Journal | Antimicrobial agents and chemotherapy |
| Date Published | 2016 Jul 5 |
| ISSN | 1098-6596 |
| 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 compared with that of wild-type. R953C mutant has a 4-fold decrease in discrimination of analog nucleotide relative to wild-type. R953 is located on the O-helix that forms substrate dNTP binding site; the interactions between R953 with E1056 and Y986 may stabilize the O-helix and affect polymerase activity. |
| DOI | 10.1128/AAC.00976-16 |
| Alternate Journal | Antimicrob. Agents Chemother. |
