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人类免疫缺陷病毒1型逆转录酶指状结构域的突变分析

Mutational analysis of the fingers domain of human immunodeficiency virus type 1 reverse transcriptase.

作者信息

Boyer P L, Ferris A L, Hughes S H

机构信息

ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201.

出版信息

J Virol. 1992 Dec;66(12):7533-7. doi: 10.1128/JVI.66.12.7533-7537.1992.

DOI:10.1128/JVI.66.12.7533-7537.1992
PMID:1279205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC240464/
Abstract

Using BspMI cassette vectors, we have constructed a series of mutations in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) that cause specific amino acid substitutions within the polymerase domain. The RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H activities of the mutant RTs were assayed. The elucidation of the structure of HIV-1 RT makes it possible to determine the locations of specific mutations in the three-dimensional structure of HIV-1 RT [E. Arnold, A. Jacobo-Molina, R. G. Nanni, R. L. Williams, X. Lu, J. Ding, A. D. Clark, Jr., A. Zhang, A. L. Ferris, P. Clark, A. Hizi, and S. H. Hughes, Nature (London) 357:85-89, 1992; L. A. Kohlstaedt, J. Wang, J. M. Friedman, P. A. Rice, and T. A. Steitz, Science 256:1783-1790, 1992]. The mutations described in this report are between amino acids 25 and 81, within the "fingers" domain of RT (Kohlstaedt et al., Science 256:1783-1790, 1992). It has been suggested that this domain may play a role in positioning the template. Although the fingers domain does not contain the active site for polymerization, several of the mutations within this domain disrupt polymerase activity without significantly affecting RNase H activity.

摘要

利用BspMI盒式载体，我们在人类免疫缺陷病毒1型（HIV-1）逆转录酶（RT）中构建了一系列突变，这些突变导致聚合酶结构域内特定氨基酸发生取代。对突变型RT的RNA依赖性DNA聚合酶、DNA依赖性DNA聚合酶和RNase H活性进行了测定。HIV-1 RT结构的阐明使得确定HIV-1 RT三维结构中特定突变的位置成为可能[E.阿诺德、A.雅各布-莫利纳、R.G.南尼、R.L.威廉姆斯、X.卢、J.丁、A.D.克拉克、A.张、A.L.费里斯、P.克拉克、A.希齐和S.H.休斯，《自然》（伦敦）357:85-89，1992；L.A.科尔施泰特、J.王、J.M.弗里德曼、P.A.赖斯和T.A.斯蒂茨，《科学》256:1783-1790，1992]。本报告中描述的突变位于RT的“手指”结构域内氨基酸25至81之间（科尔施泰特等人，《科学》256:1783-1790，1992）。有人提出该结构域可能在模板定位中起作用。虽然手指结构域不包含聚合活性位点，但该结构域内的一些突变会破坏聚合酶活性，而对RNase H活性没有显著影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a3/240464/5c6a391a72b5/jvirol00043-0711-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a3/240464/5c6a391a72b5/jvirol00043-0711-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16a3/240464/5c6a391a72b5/jvirol00043-0711-a.jpg

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