Duplex structural differences and not 2'-hydroxyls explain the more stable binding of HIV-reverse transcriptase to RNA-DNA versus DNA-DNA.
Duplex structural differences and not 2'-hydroxyls explain the more stable binding of HIV-reverse transcriptase to RNA-DNA versus DNA-DNA.
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双链体结构差异而非 2'-羟基解释了 HIV 逆转录酶与 RNA-DNA 的结合比 DNA-DNA 更稳定。
DOI：
10.1093/nar/gkq169
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发表时间：
2010-07
影响因子：
14.9
通讯作者：
DeStefano, Jeffrey J.
中科院分区：
文献类型：
--
作者：
Olimpo, Jeffrey T.;DeStefano, Jeffrey J.
人类免疫缺陷病毒逆转录酶（HIV-RT）与RNA-DNA的二元复合物比DNA-DNA更稳定。目前的研究结果表明，只有-2和-4 RNA核苷酸（-1与3′凹陷的DNA碱基杂交）是稳定结合RNA-DNA所必需的，即使是单个RNA核苷酸也比DNA-DNA具有更大的稳定性。用2′-O-甲基取代关键RNA碱基上的2′-羟基不影响稳定性，表明羟基和RT氨基酸之间的相互作用不稳定结合。DNA-DNA和RNA-DNA的RT Kd（koff/kon）相似，但koff相差近40倍，表明DNA-DNA的kon更快。禽成髓细胞瘤和莫洛尼鼠白血病病毒RT也更稳定地结合到RNA-DNA，但差异不太明显，比HIV-RT。我们建议，H-与B-型结构的RNA-DNA和DNA-DNA，分别允许前者更容易符合HIV-RT的结合裂缝，导致更稳定的结合。在生物学上，RT在RNA-DNA上形成更稳定复合物的能力可能有助于降解DNA合成后残留的RNA片段。
Human immunodeficiency virus reverse transcriptase (HIV-RT) binds more stably in binary complexes with RNA–DNA versus DNA–DNA. Current results indicate that only the -2 and -4 RNA nucleotides (-1 hybridized to the 3′ recessed DNA base) are required for stable binding to RNA–DNA, and even a single RNA nucleotide conferred significantly greater stability than DNA–DNA. Replacing 2′- hydroxyls on pivotal RNA bases with 2′-O-methyls did not affect stability, indicating that interactions between hydroxyls and RT amino acids do not stabilize binding. RT’s Kd (koff/kon) for DNA–DNA and RNA–DNA were similar, although koff differed almost 40-fold, suggesting a faster kon for DNA–DNA. Avian myeloblastosis and Moloney murine leukemia virus RTs also bound more stably to RNA–DNA, but the difference was less pronounced than with HIV-RT. We propose that the H- versus B-form structures of RNA–DNA and DNA–DNA, respectively, allow the former to conform more easily to HIV-RT’s binding cleft, leading to more stable binding. Biologically, the ability of RT to form a more stable complex on RNA–DNA may aid in degradation of RNA fragments that remain after DNA synthesis.
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影响因子：
2.9
作者：
Bohlayer, William P.;DeStefano, Jeffrey J.
通讯作者：
DeStefano, Jeffrey J.
影响因子：
4.8
作者：
DeStefano, JJ;Cristofaro, JV;Fitzgerald-Heath, MJ
通讯作者：
Fitzgerald-Heath, MJ
影响因子：
5.6
作者：
Horton, NC;Finzel, BC
通讯作者：
Finzel, BC
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
影响因子：
5
作者：
Cote, Marie L.;Roth, Monica J.
通讯作者：
Roth, Monica J.