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-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.

authors

Li M,Mislak AC,Foli Y,Agbosu E,Bose V,Bhandari S,Szymanski MR,Shumate CK,Yin YW,Anderson KS,Paintsil E

doi

10.1128/AAC.00976-16

subject

Has Abstract

pub_date

2016-08-22 00:00:00

pages

5608-11

issue

9

eissn

0066-4804

issn

1098-6596

pii

AAC.00976-16

journal_volume

60

pub_type

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