Tn5 transposase as a useful platform to simulate HIV-1 integrase inhibitor binding mode

被引：16

作者：

Barreca, Maria Letizia ^{[1
]}

Ortuso, Francesco

Iraci, Nunzio

De Luca, Laura

Alcaro, Stefano

Chimirri, Alba

机构：

[1] Univ Messina, Dipartimento Farmaco Chim, I-98168 Messina, Italy

[2] Univ Magna Gracia Catanzaro, Dipartimento Sci Farmacobiol, Lab Chim Farmaceut Computaz, I-88100 Catanzaro, Italy

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2007年 / 363卷 / 03期

关键词：

Tn5; transposase; HIV-1; integrase; beta-diketo acids (DKAs); molecular dynamics;

D O I：

10.1016/j.bbrc.2007.08.199

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 targeting of HIV-1 integrase (IN) for the design of novel antiviral compounds has until now proceeded slowly, mainly due to the lack of three-dimensional structures reporting detail interactions between IN and its DNA substrates as well as the complete enzyme with its three domains. Recently, we have proposed that Tn5 transposase (Tnp) can be used as a useful surrogate model for IN in attempt to address the potential binding modes of Integrase Strand Transfer Inhibitors. In order to strengthen our hypothesis, molecular dynamics simulations of IN inhibitors bound to Tn5 Trip active site are now reported. A comparison of the obtained results with well documented specific mutations associated with resistance to HIV-1 IN inhibitors confirmed that Tn5 Tnp can provide a valuable platform for the structure-based discovery of new ligands. (C) 2007 Elsevier Inc. All rights reserved.

引用

页码：554 / 560

页数：7

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