Entropically-driven binding of mithramycin in the minor groove of C/G-rich DNA sequences.
Entropically-driven binding of mithramycin in the minor groove of C/G-rich DNA sequences.
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DOI：
10.1093/nar/gkm037
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发表时间：
2007
影响因子：
14.9
通讯作者：
Portugal J
中科院分区：
文献类型：
--
作者：
Barceló F;Scotta C;Ortiz-Lombardía M;Méndez C;Salas JA;Portugal J
抗肿瘤抗生素光神霉素A（MTA）是一种DNA小沟结合配体。它与富含C/G的纤维束结合为二聚体，在二价阳离子如Mg 2+存在下形成。差示扫描量热法，紫外热变性，等温滴定量热法和竞争透析，连同结合的疏水自由能的计算，以确定MTA与DNA结合的热力学配置文件。将结果与使用结构相关的光辉霉素SK（MSK）平行获得的结果进行比较。在25°C下，通过UV熔解研究确定的MTA与鲑鱼睾丸DNA的结合（Kobs = 1.2（±0.3）× 105 M−1）比MSK（2.9（±1.0）× 104 M−1）更紧密。竞争透析研究表明，MTA与鲑鱼睾丸DNA（42%C + G）和溶壁微球菌DNA（72%C + G）的结合更紧密。在25°C下结合数据的热力学分析表明，MTA和MSK与DNA的结合是熵驱动的，由抗生素从溶液到DNA结合位点的疏水转移主导。MTA或MSK与DNA之间通过氢键和货车范德华接触的直接分子识别也可能显著有助于复合物的形成。
The antitumour antibiotic mithramycin A (MTA) is a DNA minor-groove binding ligand. It binds to C/G-rich tracts as a dimer that forms in the presence of divalent cations such as Mg2+. Differential scanning calorimetry, UV thermal denaturation, isothermal titration calorimetry and competition dialysis were used, together with computations of the hydrophobic free energy of binding, to determine the thermodynamic profile of MTA binding to DNA. The results were compared to those obtained in parallel using the structurally related mithramycin SK (MSK). The binding of MTA to salmon testes DNA determined by UV melting studies (Kobs = 1.2 (±0.3) × 105 M−1) is tighter than that of MSK (2.9 (±1.0) × 104 M−1) at 25°C. Competition dialysis studies showed a tighter MTA binding to both salmon testes DNA (42% C + G) and Micrococcus lysodeikticus DNA (72% C + G). The thermodynamic analysis of binding data at 25°C shows that the binding of MTA and MSK to DNA is entropically driven, dominated by the hydrophobic transfer of the antibiotics from solution to the DNA-binding site. Direct molecular recognition between MTA or MSK and DNA through hydrogen bonding and van der Waals contacts may also contribute significantly to complex formation.
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影响因子：
3.9
作者：
Chaires, Jonathan B.
通讯作者：
Chaires, Jonathan B.
DOI：
10.1073/pnas.84.24.8922
发表时间：
1987-12-01
影响因子：
11.1
作者：
BRESLAUER, KJ;REMETA, DP;MARKY, LA
通讯作者：
MARKY, LA
影响因子：
14.9
作者：
Barceló, F;Capó, D;Portugal, J
通讯作者：
Portugal, J
影响因子：
14.9
作者：
Hou, MH;Robinson, H;Wang, AHJ
通讯作者：
Wang, AHJ
影响因子：
5.6
作者：
HA, JH;SPOLAR, RS;RECORD, MT
通讯作者：
RECORD, MT