An unconventional ligand‐binding mechanism of substrate‐binding proteins: MD simulation and Markov state model analysis of BtuF
| العنوان: | An unconventional ligand‐binding mechanism of substrate‐binding proteins: MD simulation and Markov state model analysis of BtuF |
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| المؤلفون: | Wenning Wang, Dongdong Wang, Jingwei Weng |
| المصدر: | Journal of Computational Chemistry. 40:1440-1448 |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Protein Conformation, Molecular Dynamics Simulation, Crystallography, X-Ray, Ligands, 010402 general chemistry, 01 natural sciences, DNA-binding protein, Molecular dynamics, 0103 physical sciences, State model, Binding Sites, 010304 chemical physics, Markov chain, Chemistry, Escherichia coli Proteins, Binding protein, Substrate (chemistry), General Chemistry, Conformational entropy, Ligand (biochemistry), Markov Chains, 0104 chemical sciences, Kinetics, Computational Mathematics, Periplasmic Binding Proteins, Biophysics |
| الوصف: | In conventional "Venus Flytrap" mechanism, substrate-binding proteins (SBPs) interconvert between the open and closed conformations. Upon ligand binding, SBPs form a tightly closed conformation with the ligand bound at the interface of two domains. This mechanism was later challenged by many type III SBPs, such as the vitamin B12 -binding protein BtuF, in which the apo- and holo-state proteins adopt very similar conformations. Here, we combined molecular dynamics simulation and Markov state model analysis to study the conformational dynamics of apo- and B12 -bound BtuF. The results indicate that the crystal structures represent the only stable conformation of BtuF. Meanwhile, both apo- and holo-BtuF undergo large-scale interdomain motions with little energy cost. B12 binding casts little restraints on the interdomain motions, suggesting that ligand binding affinity is enhanced by the remaining conformational entropy of holo-BtuF. These results reveal a new paradigm of ligand recognition mechanism of SBPs. © 2019 Wiley Periodicals, Inc. |
| تدمد: | 1096-987X 0192-8651 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f940f61416632f45a161fef1fd7a078Test https://doi.org/10.1002/jcc.25798Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....3f940f61416632f45a161fef1fd7a078 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1096987X 01928651 |
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