Structures of reverse transcriptase pre- and post-excision complexes shed new light on HIV-1 AZT resistance.

Structures of reverse transcriptase pre- and post-excision complexes shed new light on HIV-1 AZT resistance.
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DOI:
10.3390/v3010020
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发表时间:
2011-01
期刊:
Viruses
影响因子:
--
通讯作者:
Scott WA
Scott WA
中科院分区:
其他
文献类型:
--
作者:
Scott WA

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HIV-1对3‘-叠氮-2’,3‘-脱氧胸苷(AZT,齐多夫定)的抗药性源于逆转录酶的突变,该突变增强了该酶在被掺入后清除AZT-单磷酸的能力。最近报道了野生型和突变型逆转录酶与双链DNA的复合体的晶体结构,其中包括切除产物AZT腺苷四核苷酸(AZTppA)。切除增强突变极大地改变了酶与切除产物相互作用的方式。
HIV-1 resistance to 3′-azido-2′,3′-deoxythymidine (AZT, zidovudine) results from mutations in reverse transcriptase that increase the ability of the enzyme to excise AZT-monophosphate after it has been incorporated. Crystal structures of complexes of wild type and mutant reverse transcriptase with double-stranded DNA with or without the excision product, AZT adenosine dinucleoside tetraphosphate (AZTppppA), have recently been reported. The excision-enhancing mutations dramatically change the way the enzyme interacts with the excision product.
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