Analysis of amino acids in the beta7-beta8 loop of human immunodeficiency virus type 1 reverse transcriptase for their role in virus replication.
Analysis of amino acids in the beta7-beta8 loop of human immunodeficiency virus type 1 reverse transcriptase for their role in virus replication.
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分析人类免疫缺陷病毒 1 型逆转录酶 β7-β8 环中的氨基酸在病毒复制中的作用。
DOI：
10.1016/j.jmb.2006.10.089
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发表时间：
2007
影响因子：
5.6
通讯作者：
Kappes,JohnC
中科院分区：
文献类型：
--
作者：
Mulky,Alok;Vu,BChristie;Conway,JoanA;Hughes,StephenH;Kappes,JohnC
The HIV-1 p51/p66 reverse transcriptase (RT) heterodimer interface comprises, in part, intermolecular interaction of the loop region between β-strands 7 and 8 (β7–β8 loop) in the p51 fingers subdomain with the p66 palm subdomain. In this study, for the first time in the context of infectious HIV-1 particles, we analyzed the contribution of amino acid residues (S134, I135, N136, N137, T139 and P140) in the β7–β8 loop for RT heterodimerization, enzymatic activity, and virus infectivity. Mutating asparagine 136 to alanine (N136A) reduced viral infectivity and enzyme activity dramatically. The N136A mutation appeared to destabilize the RT heterodimer and render both the p66 and p51 subunits susceptible to aberrant cleavage by the viral protease. Subunit-specific mutagenesis demonstrated that the presence of the N136A mutation in the p51 subunit alone was sufficient to cause degradation of RT within the virus particle. Alanine mutation at other residues of the β7–β8 loop did not affect either RT stability or virus infectivity significantly. None of the β7–β8 loop alanine mutations affected the sensitivity of virus to inhibition by NNRTIs. In the context of infectious virions, our results indicate a critical role of the p51 N136 residue within the β7–β8 loop for RT heterodimer stability and function. These findings suggest the interface comprising N136 in p51 and interacting residues in p66 as a possible target for rational drug design.
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HIV-1 逆转录酶聚合酶结构域内芳香族残基的色氨酸扫描诱变：Phe-130 对 p51 功能和第二位点恢复病毒复制能力的关键作用。
影响因子：
3.7
作者：
I. Olivares;M. Gutiérrez;C. López;L. Menéndez
通讯作者：
L. Menéndez
DOI：
10.1073/pnas.90.13.6320
发表时间：
1993-07-01
影响因子：
11.1
作者：
JACOBOMOLINA, A;DING, JP;ARNOLD, E
通讯作者：
ARNOLD, E
人类免疫缺陷病毒1型逆转录酶第138位氨基酸的定点诱变。
影响因子：
3.7
作者：
H. Pelemans;A. Aertsen;K. Laethem;A. Vandamme;E. Clercq;M. Pérez;A. San;S. Velázquez;M. Camarasa;J. Balzarini
通讯作者：
J. Balzarini
DOI：
10.1073/pnas.90.15.6952
发表时间：
1993-08-01
影响因子：
11.1
作者：
BALZARINI, J;KARLSSON, A;DECLERCQ, E
通讯作者：
DECLERCQ, E
影响因子：
56.9
作者：
Huang, HF;Chopra, R;Harrison, SC
通讯作者：
Harrison, SC