Identification of an amino acid in human immunodeficiency virus type 1 reverse transcriptase important in the binding of the pyrophosphate group of deoxynucleoside triphosphate (Meeting abstract).

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Identification of an amino acid in human immunodeficiency virus type 1 reverse transcriptase important in the binding of the pyrophosphate group of deoxynucleoside triphosphate (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 34:A3238 1993. Unique Identifier : AIDSLINE MED/93694194
Im GJ; Piras G; Gonzalez CJ; Cheng YC; Dept. of Pharmacology, Yale Univ. Sch. of Medicine, New Haven, CT; 06510

Abstract: A recombinant clone of human immunodeficiency virus type 1 reverse transcriptase (RT) with reduced sensitivity to AZTTP and a pyrophosphate analog phosphonoformate (PFA) has been obtained from HTLV-IIIB using the polymerase chain reaction. The inhibition constant values for AZTTP and PFA increased 10- and 3-fold, respectively, and nucleotide sequence analysis of the mutant RT revealed a single predicted amino acid substitution Lys----Asn) at codon 66. When this mutation was combined with the Cys mutation at amino acid 181 which conferred cross-resistance to the non-nucleoside RT inhibitors, the resulting mutant RT retained its resistance to AZTTP, PFA and the non-nucleoside RT inhibitors, such as nevirapine and TIBO R82150. This suggests that amino acid residue 66, together with the previously reported amino acid 90, plays a role in determining the interaction of RT enzyme with the pyrophosphate group of deoxynucleoside triphosphate.

Keywords: *Amino Acids/ANALYSIS *Foscarnet/CHEMISTRY *HIV-1/ENZYMOLOGY *RNA-Directed DNA Polymerase/CHEMISTRY *Thymine Nucleotides/CHEMISTRY *Zidovudine/ANALOGS & DERIVATIVES
931130
M93B5837

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