在HIV-1整合酶中鉴定核苷酸结合位点。
Identification of a nucleotide binding site in HIV-1 integrase.
作者信息
Drake R R, Neamati N, Hong H, Pilon A A, Sunthankar P, Hume S D, Milne G W, Pommier Y
机构信息
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4170-5. doi: 10.1073/pnas.95.8.4170.
Abstract
HIV-1 integrase is essential for viral replication and can be inhibited by antiviral nucleotides. Photoaffinity labeling with the 3'-azido-3'-deoxythymidine (AZT) analog 3',5-diazido-2', 3'-dideoxyuridine 5'-monophosphate (5N3-AZTMP) and proteolytic mapping identified the amino acid 153-167 region of integrase as the site of photocrosslinking. Docking of 5N3-AZTMP revealed the possibility for strong hydrogen bonds between the inhibitor and lysines 156, 159, and 160 of the enzyme. Mutation of these residues reduced photocrosslinking selectively. This report elucidates the binding site of a nucleotide inhibitor of HIV-1 integrase, and possibly a component of the enzyme polynucleotide binding site.
摘要
HIV-1整合酶对病毒复制至关重要，且可被抗病毒核苷酸抑制。用3'-叠氮-3'-脱氧胸苷（AZT）类似物3',5-二叠氮-2',3'-二脱氧尿苷5'-单磷酸（5N3-AZTMP）进行光亲和标记及蛋白水解图谱分析确定了整合酶的153-167氨基酸区域为光交联位点。5N3-AZTMP的对接显示该抑制剂与酶的赖氨酸156、159和160之间可能形成强氢键。这些残基的突变选择性地降低了光交联。本报告阐明了HIV-1整合酶核苷酸抑制剂的结合位点，可能也是该酶多核苷酸结合位点的一个组成部分。
相似文献
1
Identification of a nucleotide binding site in HIV-1 integrase.在HIV-1整合酶中鉴定核苷酸结合位点。
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4170-5. doi: 10.1073/pnas.95.8.4170.
2
Inhibition of human immunodeficiency virus type 1 integrase by 3'-azido-3'-deoxythymidylate.
Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5771-5. doi: 10.1073/pnas.91.13.5771.
3
Efficient gap repair catalyzed in vitro by an intrinsic DNA polymerase activity of human immunodeficiency virus type 1 integrase.由人类免疫缺陷病毒1型整合酶的内在DNA聚合酶活性在体外催化的高效缺口修复。
J Virol. 1998 Mar;72(3):2062-71. doi: 10.1128/JVI.72.3.2062-2071.1998.
4
Synthesis, anti-HIV activity and stability studies of 3'-azido-2',3'-dideoxythymidine 5'-fluorophosphate.3'-叠氮基-2',3'-双脱氧胸苷5'-氟磷酸酯的合成、抗HIV活性及稳定性研究
Nucleosides Nucleotides. 1999 Apr-May;18(4-5):983-4. doi: 10.1080/15257779908041621.
5
Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors.一种多药耐药的HIV-1 A/G亚型逆转录酶的生化特性：齐多夫定识别与切除途径的拮抗作用以及对核糖核酸酶H抑制剂的敏感性
Nucleic Acids Res. 2016 Mar 18;44(5):2310-22. doi: 10.1093/nar/gkw060. Epub 2016 Feb 4.
6
Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase.耐药性人类免疫缺陷病毒逆转录酶对阿齐硫代胸苷单磷酸的选择性切除
J Virol. 2001 May;75(10):4832-42. doi: 10.1128/JVI.75.10.4832-4842.2001.
7
3'-azido-3'-deoxythymidine (AZT) monophosphate: an inhibitor of exonucleolytic repair of AZT-terminated DNA.3'-叠氮-3'-脱氧胸苷单磷酸（AZT）：一种AZT末端DNA外切核酸酶修复的抑制剂。
Antimicrob Agents Chemother. 1993 Apr;37(4):918-20. doi: 10.1128/AAC.37.4.918.
8
Identification of the LEDGF/p75 binding site in HIV-1 integrase.HIV-1整合酶中LEDGF/p75结合位点的鉴定。
J Mol Biol. 2007 Feb 2;365(5):1480-92. doi: 10.1016/j.jmb.2006.10.094. Epub 2006 Nov 3.
9
10
NMR study of dideoxynucleotides with anti-human immunodeficiency virus (HIV) activity.具有抗人类免疫缺陷病毒（HIV）活性的双脱氧核苷酸的核磁共振研究。
J Biochem Biophys Methods. 1996 Feb 5;31(3-4):113-21. doi: 10.1016/0165-022x(95)00027-o.
引用本文的文献
1
Competitive docking model for prediction of the human nicotinic acetylcholine receptor α7 binding of tobacco constituents.用于预测烟草成分与人烟碱型乙酰胆碱受体α7结合的竞争性对接模型。
Oncotarget. 2018 Feb 8;9(24):16899-16916. doi: 10.18632/oncotarget.24458. eCollection 2018 Mar 30.
2
A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals.一种用于促进评估环境化学物质内分泌干扰潜力的大鼠甲胎蛋白结合活性预测模型。
Int J Environ Res Public Health. 2016 Mar 25;13(4):372. doi: 10.3390/ijerph13040372.
3
Comparative docking and CoMFA analysis of curcumine derivatives as HIV-1 integrase inhibitors.姜黄素衍生物作为 HIV-1 整合酶抑制剂的比较对接和 CoMFA 分析。
Mol Divers. 2011 Aug;15(3):733-50. doi: 10.1007/s11030-011-9304-7. Epub 2011 Feb 15.
4
The HIV-1 integrase α4-helix involved in LTR-DNA recognition is also a highly antigenic peptide element.HIV-1 整合酶 α4 螺旋参与 LTR-DNA 识别，也是一个高度抗原性的肽段元件。
PLoS One. 2010 Dec 30;5(12):e16001. doi: 10.1371/journal.pone.0016001.
5
Characterization of the HIV-1 integrase chromatin- and LEDGF/p75-binding abilities by mutagenic analysis within the catalytic core domain of integrase.通过在整合酶催化核心结构域内进行突变分析，对 HIV-1 整合酶与染色质和 LEDGF/p75 的结合能力进行表征。
Virol J. 2010 Mar 23;7:68. doi: 10.1186/1743-422X-7-68.
6
Specificity of LTR DNA recognition by a peptide mimicking the HIV-1 integrase {alpha}4 helix.肽模拟 HIV-1 整合酶 {alpha}4 螺旋识别 LTR DNA 的特异性。
Nucleic Acids Res. 2009 Dec;37(22):7691-700. doi: 10.1093/nar/gkp824.
7
HIV-1 IN inhibitors: 2010 update and perspectives.HIV-1 整合酶抑制剂：2010 年更新与展望。
Curr Top Med Chem. 2009;9(11):1016-37. doi: 10.2174/156802609789630910.
8
Integrase and integration: biochemical activities of HIV-1 integrase.整合酶与整合：HIV-1整合酶的生化活性
Retrovirology. 2008 Dec 17;5:114. doi: 10.1186/1742-4690-5-114.
9
Exploring the binding of HIV-1 integrase inhibitors by comparative residue interaction analysis (CoRIA).通过比较残基相互作用分析（CoRIA）探索HIV-1整合酶抑制剂的结合情况。
J Mol Model. 2009 Mar;15(3):233-45. doi: 10.1007/s00894-008-0399-4. Epub 2008 Dec 2.
10
Defining the DNA substrate binding sites on HIV-1 integrase.确定HIV-1整合酶上的DNA底物结合位点。
J Mol Biol. 2009 Jan 16;385(2):568-79. doi: 10.1016/j.jmb.2008.10.083. Epub 2008 Nov 7.
本文引用的文献
1
Retroviral integrase : a novel target in antiviral drug development and basic in vitro assays with the purified enzyme.逆转录病毒整合酶：抗病毒药物研发中的新靶点及纯化酶的基础体外试验
Methods Mol Med. 2000;24:327-38. doi: 10.1385/1-59259-245-7:327.
2
Critical contacts between HIV-1 integrase and viral DNA identified by structure-based analysis and photo-crosslinking.通过基于结构的分析和光交联鉴定出的HIV-1整合酶与病毒DNA之间的关键接触点。
EMBO J. 1997 Nov 17;16(22):6849-59. doi: 10.1093/emboj/16.22.6849.
3
Mapping features of HIV-1 integrase near selected sites on viral and target DNA molecules in an active enzyme-DNA complex by photo-cross-linking.通过光交联映射活性酶-DNA复合物中病毒和靶DNA分子上选定位点附近的HIV-1整合酶特征。
Biochemistry. 1997 Sep 2;36(35):10655-65. doi: 10.1021/bi970782h.
4
In vitro assays for activities of retroviral integrase.逆转录病毒整合酶活性的体外测定
Methods. 1997 Aug;12(4):306-17. doi: 10.1006/meth.1997.0484.
5
Probing interactions between viral DNA and human immunodeficiency virus type 1 integrase using dinucleotides.
Mol Pharmacol. 1997 Apr;51(4):567-75. doi: 10.1124/mol.51.4.567.
6
The catalytic domain of human immunodeficiency virus integrase: ordered active site in the F185H mutant.人类免疫缺陷病毒整合酶的催化结构域：F185H突变体中的有序活性位点。
FEBS Lett. 1996 Dec 2;398(2-3):175-8. doi: 10.1016/s0014-5793(96)01236-7.
7
Chemical trapping of ternary complexes of human immunodeficiency virus type 1 integrase, divalent metal, and DNA substrates containing an abasic site. Implications for the role of lysine 136 in DNA binding.1型人类免疫缺陷病毒整合酶、二价金属与含有无碱基位点的DNA底物三元复合物的化学捕获。赖氨酸136在DNA结合中作用的意义。
J Biol Chem. 1996 Nov 1;271(44):27330-8. doi: 10.1074/jbc.271.44.27330.
8
Retroviral integrases and their cousins.逆转录病毒整合酶及其同类。
Curr Opin Struct Biol. 1996 Feb;6(1):76-83. doi: 10.1016/s0959-440x(96)80098-4.
9
Proteolytic mapping of the thymidine/thymidylate binding site of herpes simplex virus type 1 thymidine kinase: a general photoaffinity labeling method for identifying active-site peptides.
Anal Biochem. 1996 May 15;237(1):135-40. doi: 10.1006/abio.1996.0211.
10
Effects of nucleotide analogues on human immunodeficiency virus type 1 integrase.核苷酸类似物对1型人类免疫缺陷病毒整合酶的影响。
Mol Pharmacol. 1996 Apr;49(4):621-8.
Zotero 插件