Conformation of a trimannoside bound to mannose-binding protein by nuclear magnetic resonance and molecular dynamics simulations.
Conformation of a trimannoside bound to mannose-binding protein by nuclear magnetic resonance and molecular dynamics simulations.
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通过核磁共振和分子动力学模拟观察三甘露糖苷与甘露糖结合蛋白结合的构象。
DOI：
10.1016/s0006-3495(02)75610-5
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发表时间：
2002
影响因子：
3.4
通讯作者：
Prestegard,JamesH
中科院分区：
文献类型：
--
作者：
Sayers,EricW;Prestegard,JamesH
提出了大鼠血清形式甘露糖结合蛋白 (MBP) 与甲基 3,6-二-O-(α-d-吡喃甘露糖基)-α-d-吡喃甘露糖苷复合的碳水化合物识别结构域模型。结合糖的允许构象源自模拟退火方案，并结合了根据转移的 NOESY 光谱计算的距离限制。然后将所得的糖构象建模为 MBP 结合位点，并在溶剂水存在的情况下使用分子动力学 (MD) 模拟来完善这些复合物模型。这些研究表明，溶液中发现的 α(1→6) 连接的两种主要构象中只有一种在束缚态 (ω=60°) 下显着填充，而 α(1→3) 连接至少采样两种状态，类似于其在自由溶液中的行为。除了其他水介导的氢键之外，结合构象还允许糖和 MBP 的 K182 之间形成直接氢键。基于结合时溶剂可及表面积的变化对候选复合物的结合常数的估计支持NMR和MD结果。这些估计进一步表明，与单糖相比，三糖中额外的糖-MBP相互作用的焓增益被熵惩罚所抵消，这为之前的结合数据提供了解释。
A model of the carbohydrate recognition domain of the serum form of mannose-binding protein (MBP) from rat complexed with methyl 3,6-di-O-(α-d-mannopyranosyl)-α-d-mannopyranoside is presented. Allowed conformations for the bound sugar were derived from simulated annealing protocols incorporating distance restraints computed from transferred NOESY spectra. The resulting sugar conformations were then modeled into the MBP binding site, and these models of the complex were refined using molecular dynamics (MD) simulations in the presence of solvent water. These studies indicate that only one of the two major conformations of theα(1→6) linkage found in solution is significantly populated in the bound state (ω=60°), whereas theα(1→3) linkage samples at least two states, similar to its behavior in free solution. The bound conformation allows direct hydrogen bonds to form between the sugar and K182 of MBP, in addition to other water-mediated hydrogen bonds. Estimates of binding constants of candidate complexes based on changes in solvent-accessible surface areas upon binding support the NMR and MD results. These estimates further suggest that the enthalpic gains of the additional sugar–MBP interactions in a trisaccharide as opposed to a monosaccharide are offset by entropic penalties, offering an explanation for previous binding data.
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DOI：
10.1136/bmj.314.7089.1225
发表时间：
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期刊：
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影响因子：
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DOI：
10.1016/b978-012733360-1/50005-1
发表时间：
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期刊：
The Journal of Physical Chemistry
影响因子：
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作者：
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影响因子：
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作者：
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