Validation of BKV large T-antigen ATP-binding site as a target for drug discovery

被引：3

作者：

Zeng, Gang ^{[1
]}

Bueno, Marta ^{[2
]}

Camachos, Carlos J. ^{[2
]}

Ramaswami, Bala ^{[1
]}

Luo, Chunqing ^{[1
]}

Randhawa, Parmjeet ^{[1
]}

机构：

[1] Univ Pittsburgh, E737 UPMC Montefiore Hosp, Dept Pathol, Div Transplant Pathol, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Dept Computat Biol, Pittsburgh, PA 15213 USA

来源：

ANTIVIRAL RESEARCH | 2009年 / 81卷 / 02期

关键词：

BK polyomavirus; Large T antigen; Drug discovery; ATP binding site; Treatment; RENAL-TRANSPLANT RECIPIENTS; LARGE TUMOR-ANTIGEN; POLYOMAVIRUS-BK; DNA-REPLICATION; IN-VITRO; SIMIAN-VIRUS-40; VIRUS; JC; NEPHROPATHY; HELICASE;

D O I：

10.1016/j.antiviral.2008.11.004

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

BK virus large T antigen (LTA) is a hexameric protein with a helicase activity that is powered by ATP hydrolysis. A mutant virus with Lys420Ala, Arg421Ala, and Asp504Ala mutations at the ATP binding sites showed marked reduction in viral fitness. This observation indicates that high throughput screening for ATPase inhibitors will be valid strategy to discover anti-BKV drugs, Pilot screening of 300 compounds from the Tim Tec ActiTarg K library identified a compound, STO18584, with selectivity index of 19.2. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：184 / 187

页数：4

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