Bending hinge

Interestingly, there are many proteins with two domains that show a very clear hinge-bending motion with an obvious functional significance. Such domains have often been reported in the literature, but were never detected on an automated basis. 

G., Berendsen, H.J.C. The essential dynamics of thermolysin Confirmation of the hinge-bending motion and comparison of simulations in vacuum and water. Proteins 22 (1995) 45-54. 

The first technique is very intuitive. Out of the few proteins that could be crystallized in a number of different conformations, adenylate kinase is probably the best-studied example. By combining nine observed crystal structures and interpolating between them, a movie was constructed that visualized a hypothetical path of its hinge-bending transition (jVonrhein et al. 1995]). 

In an early study of lysozyme ([McCammon et al. 1976]), the two domains of this protein were assumed to be rigid, and the hinge-bending motion in the presence of solvent was described by the Langevin equation for a damped harmonic oscillator. The angular displacement 0 from the equilibrium position is thus governed by... 

B. R. Brooks and M. Karplus. Normal modes for specific motions of macromolecules Application to the hinge-bending mode of lysozyme. Proc. Natl. Acad. Sci. USA, 82 4995-4999, 1985. 

Figure 4 DynDom [67] analysis of the first two normal modes of human lysozyme. Dark grey and white indicate the two dynamic domains, separated by the black hinge bending region. The vertical line represents a hinge axis that produces a closure motion in the first normal mode. The horizontal line represents a hinge axis that produces a twisting motion in the second normal mode. (Adapted from Ref. 68.) The DynDom program is available from the Internet at http //md. chem.rug.nl/ steve/dyndom.html.

Fast Tyr ring flips methyl group rotations 2. Slow hinge bending between domains ... 

As might be expected, reactivity increases with increasing structural distortion. This is conveniently measured by the hinge-bending angle, between the planes defined by the two pairs of cis substituents (e.g. R in... 

Benson DE, Conrad DW, de Lorimer RM, Trammell SA, Hallinga HW. Design of bioelectronic interfaces by exploiting hinge-bending motion of proteins. Science 2001, 293, 1641-1644. 

The internal motion of T4 lysozyme in the crystal was interpreted as an inter-domain motion corresponding to opening and closing of the active site cleft (Weaver et al., 1989). Hinge-bending and substrate-induced conformational transition in T4 lysozyme in solution were confirmed in a study by site-directed labelling (Mchaourban et al., 1997). 

Thus the above-mentioned data clearly indicate that hinge-bending (blocks) nanosecond dynamics plays a key role in protein function and in enzyme catalysis in particular. However, a detailed discussion of the problem lies beyond the scope of the present chapter, which only intends to give a general appreciation of this role. Here we are limited to considering several typical examples. 

Mchaourab, H.S., Fang, C.J, and Hubbel, W. L. (1997) Conformation of T4 lysozame in solution. Hinge bending motion and substratereduced conformational transition studied by site-directed spin labeling, Biochemistry 36, 307-316. 

Muller, Y. A., Kelley, R. F., and de Vos, A. M. (1998). Hinge bending within the cytokine receptor superfamily revealed by the 2.4 A crystal structure of the extracellular domain of rabbit tissue factor. Protein Sci. 7, 1106-1115. 

A physical technique for the study of conformation based on measuring changes in heat capacity of a molecule under various conditions. See Zecchinon, L., Oriol, A., Netzel, U. et al.. Stability domains, substrate-induced conformational changes, and hinge-bending motions in a psychro-philic phosphoglycerate kinase. A microcalorimetric study, J. Biol. Chem. 280, 41307-41314, 2005. 

Neutron spectroscopy is becoming a principal tool for the study of protein dynamics (Cusack, 1986, 1989 Middendorf, 1984 Middendorf et al., 1984). Current instruments cover motions with characteristic times from 10 to 10 sec. This range embraces essentially all protein modes excited at room temperature (the soft modes), including motions of the solvent shell and also low-frequency large-scale domain motions, like the hinge-bending motion of the lysozyme domains that form the... 

Comparison of neutron scattering of lysozyme at 0.07 and 0.20 h (Smith et al., 1987) showed that hydration decreased elastic scattering and increased inelastic scattering between 0.8 and 4.0 cm". This observation is consistent with an increase in the number of low-frequency modes. Normal mode analysis indicates that the lowest frequency mode of lysozyme and the hinge-bending mode fall in this frequency range (Brooks and Karplus, 1985 Bruccoleri et al., 1986 Levitt et al., 1985). Hydration of a protein has little effect on the scattering spectrum, outside of that noted above (Cusack, 1989). 

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