Jacobo-Molina A, Arnold E
Center for Advanced Biotechnology and Medicine (CABM), Rutgers University, Piscataway, New Jersey 08854-5638.
Biochemistry. 1991 Jul 2;30(26):6351-6. doi: 10.1021/bi00240a001.
HIV reverse transcriptase (RT) is the target of the most widely used treatments for AIDS. Biochemical and mutagenesis studies performed on HIV-1 RT are reviewed in light of the enzyme's structure and functions. Features described include domain arrangement, dimerization, proteolytic processing, and specific recognition of the priming tRNA. Possible regions of functional importance as determined by comparative amino acid sequence analysis and by site-directed mutagenesis are identified. Among the conclusions of the analysis is the unexpected realization that the substrate for proteolytic maturation of the HIV-1 RT p66/p66 homodimer to the p66/p51 heterodimer is most likely an unfolded RNase H domain. In addition, the current progress in crystallization and structure determination of HIV-1 RT is described. Finally, a functional-model of the active reverse transcription complex is presented.
HIV逆转录酶（RT）是治疗艾滋病最广泛使用的药物的靶点。鉴于该酶的结构和功能，对HIV-1 RT进行的生化和诱变研究进行了综述。所描述的特征包括结构域排列、二聚化、蛋白水解加工以及对引发tRNA的特异性识别。通过比较氨基酸序列分析和定点诱变确定了可能具有功能重要性的区域。分析得出的结论之一是意外发现HIV-1 RT p66/p66同型二聚体蛋白水解成熟为p66/p51异型二聚体的底物很可能是一个未折叠的核糖核酸酶H结构域。此外，还描述了HIV-1 RT结晶和结构测定的当前进展。最后，提出了活性逆转录复合物的功能模型。
