A hierarchy of timescales in protein dynamics is linked to enzyme catalysis

Henzler-Wildman, Katherine A.; Ming Lei; Vu Thai; Kerns, S. Jordan; Karplus, Martin; Kern, Dorothee
December 2007
Nature;12/6/2007, Vol. 450 Issue 7171, p913
Academic Journal
The synergy between structure and dynamics is essential to the function of biological macromolecules. Thermally driven dynamics on different timescales have been experimentally observed or simulated, and a direct link between micro- to milli-second domain motions and enzymatic function has been established. However, very little is understood about the connection of these functionally relevant, collective movements with local atomic fluctuations, which are much faster. Here we show that pico- to nano-second timescale atomic fluctuations in hinge regions of adenylate kinase facilitate the large-scale, slower lid motions that produce a catalytically competent state. The fast, local mobilities differ between a mesophilic and hyperthermophilic adenylate kinase, but are strikingly similar at temperatures at which enzymatic activity and free energy of folding are matched. The connection between different timescales and the corresponding amplitudes of motions in adenylate kinase and their linkage to catalytic function is likely to be a general characteristic of protein energy landscapes.


Related Articles

  • Physical Mechanisms and Biological Significance of Supramolecular Protein Self-Assembly. Kentsis, Alex; Borden, Katherine L. B. // Current Protein & Peptide Science;Apr2004, Vol. 5 Issue 2, p125 

    In living cells, chemical reactions of metabolism, information processing, growth and development are organized in a complex network of interactions. At least in pail, the organization of this network is accomplished as a result of physical assembly by supramolecular scaffolds. Indeed, most...

  • Catalytic properties of supramolecular systems based on polyoxyethylated calixarenes and amines. Mirgorodskaya, A.; Yatskevich, E.; Kudryashova, Yu.; Solov'eva, S.; Antipin, I.; Zakharova, L.; Konovalov, A. // Kinetics & Catalysis;Jul2011, Vol. 52 Issue 4, p529 

    The rate of carboxylic ester cleavage by amphiphilic low-molecular-weight and polymeric amines in the presence of polyoxyethylated calix[4]arenes with different degrees of oxyethylation is determined by the formation of mixed aggregates, by the shift of p K of the amine, and the character of the...

  • The Use of Calixarenes in Asymmetric Catalysis. Zheng-Yi Li; Jia-Wen Chen; Ying Liu; Wei Xia; Leyong Wang // Current Organic Chemistry;Jan2011, Vol. 15 Issue 1, p39 

    No abstract available.

  • Host-induced Chemical Control: Supramolecular Catalysis Based on the Host--Guest Interaction of Cucurbit[n]urils. Hang Cong; Zhu Tao; Sai-Feng Xue; Qian-Jiang Zhu // Current Organic Chemistry;Jan2011, Vol. 15 Issue 1, p86 

    No abstract available.

  • Chemistry inside molecular containers in the gas phase. Lee, Tung-Chun; Kalenius, Elina; Lazar, Alexandra I.; Assaf, Khaleel I.; Kuhnert, Nikolai; Grün, Christian H.; Jänis, Janne; Scherman, Oren A.; Nau, Werner M. // Nature Chemistry;May2013, Vol. 5 Issue 5, p376 

    Inner-phase chemical reactions of guest molecules encapsulated in a macromolecular cavity give fundamental insight into the relative stabilization of transition states by the surrounding walls of the host, thereby modelling the situation of substrates in enzymatic binding pockets. Although in...

  • A Switchable Gold Catalyst by Encapsulation in a Self-Assembled Cage. Jans, Anne C. H.; Gómez‐Suárez, Adrián; Nolan, Steven P.; Reek, Joost N. H. // Chemistry - A European Journal;10/10/2016, Vol. 22 Issue 42, p14836 

    Dinuclear gold complexes have the ability to interact with one or more substrates in a dual-activation mode, leading to different reactivity and selectivity than their mononuclear relatives. In this contribution, this difference was used to control the catalytic properties of a gold-based...

  • Beyond Relationships Between Homogeneous and Heterogeneous Catalysis. Dixon, David; Katz, Alexander; Arslan, Ilke; Gates, Bruce // Catalysis Letters;Nov2014, Vol. 144 Issue 11, p1785 

    Graphical Abstract: [Figure not available: see fulltext.]

  • Perturbation Theory in the Catalytic Rate Constant of the Henri-Michaelis-Menten Enzymatic Reaction. Bakalis, Evangelos; Kosmas, Marios; Papamichael, Emmanouel // Bulletin of Mathematical Biology;Nov2012, Vol. 74 Issue 11, p2535 

    The Henry-Michaelis-Menten (HMM) mechanism of enzymatic reaction is studied by means of perturbation theory in the reaction rate constant k of product formation. We present analytical solutions that provide the concentrations of the enzyme ( E), the substrate ( S), as well as those of the...

  • Modeling of solvent flow effects in enzyme catalysis under physiological conditions. Schofield, Jeremy; Inder, Paul; Kapral, Raymond // Journal of Chemical Physics;5/28/2012, Vol. 136 Issue 20, p205101 

    A stochastic model for the dynamics of enzymatic catalysis in explicit, effective solvents under physiological conditions is presented. Analytically-computed first passage time densities of a diffusing particle in a spherical shell with absorbing boundaries are combined with densities obtained...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics