Second-contact shell mutation diminishes streptavidin-biotin binding affinity through transmitted effects on equilibrium dynamics.
Second-contact shell mutation diminishes streptavidin-biotin binding affinity through transmitted effects on equilibrium dynamics.
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DOI：
10.1021/bi201221j
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发表时间：
2012-01-17
期刊：
影响因子：
2.9
通讯作者：
Lybrand, Terry P.
中科院分区：
文献类型：
--
作者：
Baugh, Loren;Isolde Le Trong;Cerutti, David S.;Mehta, Nital;Guelich, Susanne;Stayton, Patrick S.;Stenkamp, Ronald E.;Lybrand, Terry P.
We report a point mutation in the second contact shell of the high-affinity streptavidin-biotin complex that appears to reduce binding affinity through transmitted effects on equilibrium dynamics. The Y54F streptavidin mutation causes a 75-fold loss of binding affinity with 73-fold faster dissociation, a large loss of binding enthalpy (ΔΔH, 3.4 kcal/mol at 37 °C) and a small gain in binding entropy (TΔΔS, 0.7 kcal/mol). The removed Y54 hydroxyl is replaced by a water molecule in the bound structure, but there are no observable changes in structure in the first contact shell and no additional changes surrounding the mutation. Molecular dynamics simulations reveal a large increase in atomic fluctuations for W79, a key biotin contact residue, compared to the wild type complex. The increased W79 fluctuations are caused by loss of water-mediated hydrogen bonds between the Y54 hydroxyl group and peptide backbone atoms in and near W79. We propose that the increased fluctuations diminish the integrity of the W79-biotin interaction and represent a loosening of the “tryptophan collar” which is critical to the slow dissociation and high affinity of streptavidin-biotin binding. These results illustrate how changes in protein dynamics distal to the ligand binding pocket can have a profound impact on ligand binding, even when equilibrium structure is unperturbed.
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DOI：
10.1107/s0907444904019158
发表时间：
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影响因子：
2.2
作者：
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通讯作者：
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影响因子：
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影响因子：
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