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M9470107.TXT
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1994-07-02
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Document 0107
DOCN M9470107
TI Subunit-selective mutagenesis of Glu-89 residue in human
immunodeficiency virus reverse transcriptase. Contribution of p66 and
p51 subunits to nucleoside analog sensitivity, divalent cation
preference, and steady state kinetic properties.
DT 9409
AU Kew Y; Qingbin S; Prasad VR; Department of Microbiology and Immunology,
Albert Einstein; College of Medicine, New York, New York 10461.
SO J Biol Chem. 1994 May 27;269(21):15331-6. Unique Identifier : AIDSLINE
MED/94253100
AB The E89G alteration in the human immunodeficiency virus type 1 reverse
transcriptase has been shown to confer resistance to nucleoside analogs
and a loss of magnesium cation preference (Prasad, V.R., Lowy, I., De
Los Santos, T., Chiang, L., and Goff, S.P. (1991) Proc. Natl. Acad. Sci.
U.S.A. 88, 11363-11367. The wild type reverse transcriptase heterodimer,
chimeric reverse transcriptases that contain the E89G alteration in one
of the subunits (p66wt/p51m and p66m/p51wt), and the mutant enzyme
(p66m/p51m) were prepared. Analysis of steady state kinetic parameters
showed that the mutant enzyme (p66m/p51m) displayed a higher Vmax, a
higher Km for 2'-deoxythymidine triphosphate, and a higher Ki for
2',3'-dideoxythymidine triphosphate than the wild type enzyme. The
increased Km and Ki values were observed only when a heterodimer
contained the alteration in the p66 subunit. Tests for divalent cation
requirement showed that only the dimers containing the wild type p66
(p66wt/p51wt and p66wt/p51m) displayed a preference for magnesium. Our
results indicate that p66 plays a dominant role in deoxynucleotide
triphosphate substrate recognition (Km), nucleoside analog sensitivity
(Ki), and magnesium preference. However, the increased Vmax displayed by
the mutant enzyme (p66m/p51m) appeared to be determined by both of the
subunits.
DE Base Sequence Cations, Divalent/METABOLISM DNA Primers
Foscarnet/PHARMACOLOGY Glutamates/*GENETICS Human HIV-1/DRUG
EFFECTS/*ENZYMOLOGY/GENETICS Kinetics Molecular Sequence Data
*Mutagenesis, Site-Directed Reverse Transcriptase/ANTAGONISTS &
INHIB/CHEMISTRY/*GENETICS Support, Non-U.S. Gov't Support, U.S. Gov't,
P.H.S. Thymine Nucleotides/PHARMACOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).