The dynamical response of hen egg white lysozyme to the binding of a carbohydrate ligand
Abstract
It has become clear that the binding of small and large ligands to proteins can invoke significant changes in side chain and main chain motion in the fast picosecond to nanosecond timescale. Recently, the use of a “dynamical proxy” has indicated that changes in these motions often reflect significant changes in conformational entropy. These entropic contributions are sometimes of the same order as the total entropy of binding. Thus, it is important to understand the connections amongst motion between the manifold of states accessible to the native state of proteins, the corresponding entropy, and how this impacts the overall energetics of protein function. The interaction of proteins with carbohydrate ligands is central to a range of biological functions. Here, we examine a classic carbohydrate interaction with an enzyme: the binding of wild‐type hen egg white lysozyme (HEWL) to the natural, competitive inhibitor chitotriose. Using NMR relaxation experiments, backbone amide and side chain methyl axial order parameters were obtained across apo and chitotriose‐bound HEWL. Upon binding, changes in the apparent amplitude of picosecond to nanosecond main chain and side chain motions are seen across the protein. Indeed, binding of chitotriose renders a large contiguous fraction of HEWL effectively completely rigid. Changes in methyl flexibility are most pronounced closest to the binding site, but average to only a small overall change in the dynamics across the protein. The corresponding change in conformational entropy is unfavorable and estimated to be a significant fraction of the total binding entropy.
Number of times cited: 13
- Fei‐He Ma, Xiao Wang, Jia‐Liang Chen, Xin Wen, Han Sun and Xun‐Cheng Su, Deciphering the Multisite Interactions of a Protein and Its Ligand at Atomic Resolution by Using Sensitive Paramagnetic Effects, Chemistry – A European Journal, 23, 4, (926-934), (2016).
- Holger Gohlke, Ido Y. Ben-Shalom, Hannes Kopitz, Stefania Pfeiffer-Marek and Karl-Heinz Baringhaus, Rigidity Theory-Based Approximation of Vibrational Entropy Changes upon Binding to Biomolecules, Journal of Chemical Theory and Computation, 10.1021/acs.jctc.7b00014, 13, 4, (1495-1502), (2017).
- Katherine A. Niessen, Mengyang Xu, Alessandro Paciaroni, Andrea Orecchini, Edward H. Snell and Andrea G. Markelz, Moving in the Right Direction: Protein Vibrations Steering Function, Biophysical Journal, 10.1016/j.bpj.2016.12.049, 112, 5, (933-942), (2017).
- Evan S. O'Brien, A. Joshua Wand and Kim A. Sharp, On the ability of molecular dynamics force fields to recapitulate NMR derived protein side chain order parameters, Protein Science, 25, 6, (1156-1160), (2016).
- Kyle W. Harpole, Evan S. O'Brien, Matthew A. Clark, C. James McKnight, Liliya Vugmeyster and A. Joshua Wand, The unusual internal motion of the villin headpiece subdomain, Protein Science, 25, 2, (423-432), (2015).
- Yuyu Yao, Michele R. Richards, Elena N. Kitova and John S. Klassen, Influence of Sulfolane on ESI-MS Measurements of Protein–Ligand Affinities, Journal of The American Society for Mass Spectrometry, 10.1007/s13361-015-1312-x, 27, 3, (498-506), (2015).
- Asmit Bhowmick and Teresa Head-Gordon, A Monte Carlo Method for Generating Side Chain Structural Ensembles, Structure, 10.1016/j.str.2014.10.011, 23, 1, (44-55), (2015).
- Laura Ragona, Katiuscia Pagano, Simona Tomaselli, Filippo Favretto, Alberto Ceccon, Serena Zanzoni, Mariapina D'Onofrio, Michael Assfalg and Henriette Molinari, The role of dynamics in modulating ligand exchange in intracellular lipid binding proteins, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 10.1016/j.bbapap.2014.04.011, 1844, 7, (1268-1278), (2014).
- Alan C. Gibbs, Elements and Modulation of Functional Dynamics, Journal of Medicinal Chemistry, 10.1021/jm500325k, 57, 19, (7819-7837), (2014).
- Dennis C. Glass, Marimuthu Krishnan, Jeremy C. Smith and Jerome Baudry, Three Entropic Classes of Side Chain in a Globular Protein, The Journal of Physical Chemistry B, 10.1021/jp400564q, 117, 11, (3127-3134), (2013).
- Vignesh Kasinath, Kim A. Sharp and A. Joshua Wand, Microscopic Insights into the NMR Relaxation-Based Protein Conformational Entropy Meter, Journal of the American Chemical Society, 10.1021/ja405200u, 135, 40, (15092-15100), (2013).
- John T. King and Kevin J. Kubarych, Site-Specific Coupling of Hydration Water and Protein Flexibility Studied in Solution with Ultrafast 2D-IR Spectroscopy, Journal of the American Chemical Society, 10.1021/ja307401r, 134, 45, (18705-18712), (2012).
- David A. Turton, Hans Martin Senn, Thomas Harwood, Adrian J. Lapthorn, Elizabeth M. Ellis and Klaas Wynne, Terahertz underdamped vibrational motion governs protein-ligand binding in solution, Nature Communications, 10.1038/ncomms4999, 5, (2014).
