Hinge-bending motions

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. 

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... 

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. 

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. 

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... 

By attaching a donor-acceptor TMR/Texas Red pair of dye molecules site-specifically to noninterfering sites on the enzyme (Fig. 24.1a) [12], we were able to measure the hinge-bending motions of the enzyme by monitoring the donor-acceptor emission intensities (Fig. 24.1b) as a function of time. We estimated the Forster distance Rq [19] of a TMR/Texas Red pair to be about... 

Figure 24.2a shows dual fluorescence intensity trajectories simultaneously recorded from a donor-acceptor labeled T4 lysozyme in the presence of substrate at pH 7.2. The anticorrelated fluctuations (Fig. 24.2a and b) are due to spFRET, reporting the donor-acceptor distance change associated with the protein conformational motion. Likewise, fluorescence trajectories of donor-acceptor labeled T4 lysozyme without substrates did not show anticorrelated behavior (Fig. 24.2c and d). We attribute this conformational motion to an enzymatic-related motion, most likely the open-closed hinge-bending motion... 

E-fS ES ES. The standard deviation of the distribution, (Atopen ) = 8.3 2ms, reflects the distribution bandwidth. For the individual T4 lysozyme molecules examined under the same enz unatic reaction conditions, we found that the first and second moments of the single-molecule topen distributions are homogeneous, within the error bars. The hinge-bending motion allows sufficient structural flexibility for the enzyme to optimize its domain conformation the donor fluorescence essentially reaches the same intensity in each turnover, reflecting the domain conformation reoccurrence. The distribution with a defined first moment and second moment shows typical oscillatory conformational motions. The nonequilibrium conformational motions in forming the active enzymatic reaction intermediate states intrinsically define a recurrence of the essentially similar potential surface for the enzymatic reaction to occur, which represents a memory effect in the enzymatic reaction conformational dynamics [12,41,42]. 

We model the hinge-bending motion associated with interactions between the enzyme and substrate as a classical particle one-dimensional multiple-step random walk in the presence of a force field [12,24], n(f), where n t) is the step index (Fig. 24.7). The position distribution density function Pn t) can be calculated [12] by... 

The normal mode calculation of the hinge bending motion does not require the definition of a rotation axis. An iterative procedure (Brooks and Karplus 1985)... 

Marques, O. and Sanejouand, Y.-H. (1995) Hinge-Bending Motion in Citrate Synthase Arising From Normal Mode Calculations, Proteins Struct. Fund. Genet. 23, 557-560. 

B. Sandak, H. J. Wolfson, and R. Nussinov. Hinge-bending motion at molecular interfaces Computerized docking of a dihydroxyethylene-containing inhibitor to the hiv-1 protease. Journal of Biomolecular Structure and Dynamics, 1 233-252, 1996. 

---