Statistical Time Events in Enzymes: A Physical Assessmen

Careri, G.; Fasella, P.; Gratton, Enrico; Jencks, William P.

doi:10.3109/10409237509102555

Cited by 200 publications

(85 citation statements)

References 89 publications

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“…Fluctuations permit conformational motions (34,35), for instance, flips of the side chains and motions of the backbone, thus causing transitions among the substates (36). Slaving, the fact that many protein fluctuations occur with the temperature dependence of the solvent fluctuations, implies that the solvent fluctuations overwhelm the intrinsic fluctuations of the protein and the hydration shell.…”

Section: Solvent Fluctuations Are Responsible For Slavingmentioning

confidence: 99%

Slaving: Solvent fluctuations dominate protein dynamics and functions

Fenimore

Frauenfelder

McMahon

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

637

558

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Protein motions are essential for function. Comparing protein processes with the dielectric fluctuations of the surrounding solvent shows that they fall into two classes: nonslaved and slaved. Nonslaved processes are independent of the solvent motions; their rates are determined by the protein conformation and vibrational dynamics. Slaved processes are tightly coupled to the solvent; their rates have approximately the same temperature dependence as the rate of the solvent fluctuations, but they are smaller. Because the temperature dependence is determined by the activation enthalpy, we propose that the solvent is responsible for the activation enthalpy, whereas the protein and the hydration shell control the activation entropy through the energy landscape. Bond formation is the prototype of nonslaved processes; opening and closing of channels are quintessential slaved motions. The prevalence of slaved motions highlights the importance of the environment in cells and membranes for the function of proteins.. . . everything that living things do can be understood in terms of the jigglings and wigglings of atoms.R. P. Feynman (1) P roteins perform most of the functions of living things, from metabolism to thinking. Textbooks usually show proteins naked, neglect fluctuations, and take little notice of the protein environment. Real proteins, however, are wiggling and jiggling, dressed by the hydration shell, and embedded in a cell or cell membrane. Feynman (1) stated the central problem succinctly, namely understanding protein functions in terms of the atomic motions. We are still very far from this goal, but progress is being made. Here we consider the effect of solvent fluctuations on protein processes. We will show that protein motions can be nonslaved or slaved. Nonslaved motions are independent of the solvent fluctuations. Slaved motions have rates that are proportional to the fluctuation rate of the solvent, but are smaller. We introduce a model, based on the energy landscape of the protein, that suggests how the protein controls its slaved dynamics. We use myoglobin (Mb) as a prototype, but the concepts apply also to many other proteins. The Dichotomy of MotionsThe main result of the present article emerges when the temperature dependences of protein processes are compared with the dielectric relaxation rate coefficient k diel (T) (2) of the solvent, essentially the average tumbling rate of the solvent water molecules. Fig. 1 shows k diel (T) (2) and the rate coefficients for various processes in Mb embedded in a 3:1 (vol͞vol) glycerol͞ water solvent (3-7). [We do not consider vibrations here, which can be described by normal modes (8).] We characterize the rate coefficients for selected processes by using the Inset in Fig. 1. The Inset shows a cross section through part of Mb with a heme group situated in the heme cavity and a major cavity called Xe-1 and labeled D. Small ligands such as carbon monoxide (CO) bind covalently at the heme iron. We denote the position of the CO by S if it is in the solvent, by A i...

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Section: Solvent Fluctuations Are Responsible For Slavingmentioning

confidence: 99%

Slaving: Solvent fluctuations dominate protein dynamics and functions

Fenimore

Frauenfelder

McMahon

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

637

558

View full text Add to dashboard Cite

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“…The possible functional importance of protein dynamics in enzyme catalysis and ligand-binding processes is an area of active interest [1][2][3][4][5]. The wealth of structural and kinetic data on the heme-binding proteins, myoglobin and hemoglobin, and the likely importance of dynamic processes in these proteins have prompted us to investigate dynamic aspects of the heme-binding site in two distinct apomyoglobin-fluorophore conjugates.…”

Section: Introductionmentioning

confidence: 99%

Dynamic aspects of the heme-binding site in phylogenetically distant myoglobins

Bismuto¹,

Irace²,

Colonna³

et al. 1987

Biochimica et Biophysica Acta (BBA) - Protein Structure and Mol

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“…However, proteins are inherently unstable, and the rate of transition from the folded to the unfolded state is relatively rapid. Moreover, protein molecules also undergo relatively large fluctuations in internal energy, which are reflected by conformational fluctuations (1)(2)(3). The use of therapeutic proteins, such as erythropoietin and tissue plasminogen activator, has recently revolutionized the treatment of many diseases, and many other proteins are expected to become available for therapeutic use in the future (4,5).…”

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confidence: 99%