人免疫缺陷病毒1型逆转录酶的核苷类似物耐药变体E89G的聚合酶保真度增加。
Increased polymerase fidelity of E89G, a nucleoside analog-resistant variant of human immunodeficiency virus type 1 reverse transcriptase.
作者信息
Drosopoulos W C, Prasad V R
机构信息
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
出版信息
J Virol. 1996 Jul;70(7):4834-8. doi: 10.1128/JVI.70.7.4834-4838.1996.
Abstract
Nucleoside analog resistance in human immunodeficiency virus type 1 results from mutations in reverse transcriptase (RT) that allow the enzyme to discriminate against such analogs. To evaluate the possible impact of such mutations on the ability of human immunodeficiency virus RT to selectively incorporate Watson-Crick base-paired deoxynucleotide triphosphates (dNTPs) over incorrectly paired dNTPs, we have measured the fidelity of dNTP insertion by the E89G variant of RT in in vitro reaction mixtures containing synthetic template primers. The E89G RT was previously shown to be resistant to several ddNTPs and to phosphonoformic acid. Our results show that the mutant enzyme displays a lower level of efficiency of misinsertion than did the wild-type RT for every mispair tested (ranging from 2- to 17-fold.
摘要
1型人类免疫缺陷病毒中的核苷类似物耐药性是由逆转录酶（RT）中的突变引起的，这些突变使该酶能够区分此类类似物。为了评估此类突变对人类免疫缺陷病毒RT选择性掺入沃森-克里克碱基配对脱氧核苷三磷酸（dNTP）而非错误配对dNTP能力的可能影响，我们在含有合成模板引物的体外反应混合物中测量了RT的E89G变体插入dNTP的保真度。先前已证明E89G RT对几种双脱氧核苷三磷酸和膦甲酸具有抗性。我们的结果表明，对于所测试的每一种错配（范围为2至17倍），突变酶的错掺入效率水平均低于野生型RT。
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本文引用的文献
1
Role of methionine 184 of human immunodeficiency virus type-1 reverse transcriptase in the polymerase function and fidelity of DNA synthesis.
Biochemistry. 1996 Feb 20;35(7):2168-79. doi: 10.1021/bi9516642.
2
Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase.
Science. 1996 Mar 1;271(5253):1282-5. doi: 10.1126/science.271.5253.1282.
3
Gel fidelity assay measuring nucleotide misinsertion, exonucleolytic proofreading, and lesion bypass efficiencies.
Methods Enzymol. 1995;262:232-56. doi: 10.1016/0076-6879(95)62021-4.
4
The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine.
Antimicrob Agents Chemother. 1993 Jun;37(6):1390-2. doi: 10.1128/AAC.37.6.1390.
5
Changes in drug sensitivity of human immunodeficiency virus type 1 during therapy with azidothymidine, dideoxycytidine, and dideoxyinosine: an in vitro comparative study.
Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):562-6. doi: 10.1073/pnas.90.2.562.
6
HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy.
Science. 1995 Jan 27;267(5197):483-9. doi: 10.1126/science.7824947.
7
Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4. doi: 10.1073/pnas.90.13.6320.
8
Reduced frameshift fidelity and processivity of HIV-1 reverse transcriptase mutants containing alanine substitutions in helix H of the thumb subdomain.
J Biol Chem. 1995 Aug 18;270(33):19516-23. doi: 10.1074/jbc.270.33.19516.
9
Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase.
Biochemistry. 1995 May 30;34(21):7207-16. doi: 10.1021/bi00021a036.
10
Locations of anti-AIDS drug binding sites and resistance mutations in the three-dimensional structure of HIV-1 reverse transcriptase. Implications for mechanisms of drug inhibition and resistance.
J Mol Biol. 1994 Oct 28;243(3):369-87. doi: 10.1006/jmbi.1994.1665.
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