THE REVERSE-TRANSCRIPTASE OF HIV-1 - FROM ENZYMOLOGY TO THERAPEUTIC INTERVENTION

被引:24
作者
TARRAGOLITVAK, L [1 ]
ANDREOLA, ML [1 ]
NEVINSKY, GA [1 ]
SARIHCOTTIN, L [1 ]
LITVAK, S [1 ]
机构
[1] CNRS,INST BIOCHIM CELLULAIRE,REPLICAT & EXPRESS GENOMES EUCARYOTES & RETROVIRA,F-33077 BORDEAUX,FRANCE
关键词
STRUCTURE-FUNCTIONAL STUDIES; 3-D STRUCTURE; INHIBITORS;
D O I
10.1096/fasebj.8.8.7514143
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS. Replication of this virus requires the activity of a retrovirus encoded RNA-dependent DNA polymerase, or reverse transcriptase (RT). HIV-1 RT is required for the synthesis of the double-stranded proviral DNA from the single-stranded retroviral RNA genome. HIV-1. RT has two subunits of 66 kDa and 51 kDa. The 66-kDa subunit contains the DNA polymerase and RNase H domains whereas the 51-kDa subunit, obtained by proteolytic maturation of the former subunit, has only the DNA synthetic activity. Two recently reported crystal structures of HIV-1 RT have revealed the very asymmetric structure of this molecule. In addition to providing information concerning the mechanism of nucleic acid polymerization, biochemical and biophysical studies of this enzyme are providing key insights for the design of selective antiviral agents. The multiple activities displayed by reverse transcriptase in the replication of the retroviral genome ensure that this enzyme will remain at the forefront of antiviral strategies in the fight against AIDS and other retrovirus-related pathologies.
引用
收藏
页码:497 / 503
页数:7
相关论文
共 62 条
[1]   AFFINITY LABELING AND FUNCTIONAL-ANALYSIS OF THE PRIMER BINDING DOMAIN OF HIV-1 REVERSE-TRANSCRIPTASE [J].
ANDREOLA, ML ;
TARRAGOLITVAK, L ;
LEVINA, AS ;
KOLOCHEVA, TI ;
ELDIRANIDIAB, R ;
JAMKOVOY, VI ;
KHALIMSKAYA, NL ;
BARR, PJ ;
LITVAK, S ;
NEVINSKY, GA .
BIOCHEMISTRY, 1993, 32 (14) :3629-3637
[2]  
ANDREOLA ML, 1992, J BIOL CHEM, V267, P19356
[3]   STRUCTURE OF HIV-1 REVERSE-TRANSCRIPTASE DNA COMPLEX AT 7-A RESOLUTION SHOWING ACTIVE-SITE LOCATIONS [J].
ARNOLD, E ;
JACOBOMOLINA, A ;
NANNI, RG ;
WILLIAMS, RL ;
LU, XD ;
DING, JP ;
CLARK, AD ;
ZHANG, AQ ;
FERRIS, AL ;
CLARK, P ;
HIZI, A ;
HUGHES, SH .
NATURE, 1992, 357 (6373) :85-89
[4]   VIRAL RNA-DEPENDENT DNA POLYMERASE - RNA-DEPENDENT DNA POLYMERASE IN VIRIONS OF RNA TUMOUR VIRUSES [J].
BALTIMORE, D .
NATURE, 1970, 226 (5252) :1209-+
[5]   HIV-1 REVERSE-TRANSCRIPTASE SPECIFICALLY INTERACTS WITH THE ANTICODON DOMAIN OF ITS COGNATE PRIMER TRANSFER-RNA [J].
BARAT, C ;
LULLIEN, V ;
SCHATZ, O ;
KEITH, G ;
NUGEYRE, MT ;
GRUNINGERLEITCH, F ;
BARRESINOUSSI, F ;
LEGRICE, SFJ ;
DARLIX, JL .
EMBO JOURNAL, 1989, 8 (11) :3279-3285
[6]   CHARACTERIZATION OF THE DOUBLE-STRANDED-RNA DEPENDENT RNASE ACTIVITY ASSOCIATED WITH RECOMBINANT REVERSE TRANSCRIPTASES [J].
BENARTZI, H ;
ZEELON, E ;
LEGRICE, SFJ ;
GORECKI, M ;
PANET, A .
NUCLEIC ACIDS RESEARCH, 1992, 20 (19) :5115-5118
[7]   MECHANISMS OF THE INHIBITION OF REVERSE TRANSCRIPTION BY ANTISENSE OLIGONUCLEOTIDES [J].
BOIZIAU, C ;
THUONG, NT ;
TOULME, JJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (02) :768-772
[8]   INVITRO EFFECT OF ANTISENSE OLIGONUCLEOTIDES ON HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE TRANSCRIPTION [J].
BORDIER, B ;
HELENE, C ;
BARR, PJ ;
LITVAK, S ;
SARIHCOTTIN, L .
NUCLEIC ACIDS RESEARCH, 1992, 20 (22) :5999-6006
[9]   INHIBITION OF THE P66/P51 FORM OF HUMAN-IMMUNODEFICIENCY-VIRUS REVERSE-TRANSCRIPTASE BY TRANSFER RNALYS [J].
BORDIER, B ;
TARRAGOLITVAK, L ;
SALLAFRANQUEANDREOLA, ML ;
ROBERT, D ;
THARAUD, D ;
FOURNIER, M ;
BARR, PJ ;
LITVAK, S ;
SARIHCOTTIN, L .
NUCLEIC ACIDS RESEARCH, 1990, 18 (03) :429-436
[10]  
Champoux J.J., 1993, REVERSE TRANSCRIPTAS, P103