Switch conformation

Coiled Coils Designed to Switch Conformational State (2002 and 2003)... 

Vyacheslav V. Samoshin was born in Norilsk, Russian Federation. He graduated with an Honorable Diploma (M.S.) from Moscow State University in 1974. At the same university, he defended his Ph.D. dissertation under the supervision of academician Nikolay S. Zefirov in 1982, and his Doctor of Chemical Sciences dissertation in 1991. He worked as a researcher in the Department of Chemistry, Moscow State University, and since 1992 as professor (head of the Division of Organic Chemistry in Moscow State Academy of Fine Chemical Technology). In 1999, he took his present position as professor of chemistry at the University of the Pacific, Stockton, California. His scientific interests include molecular switches, conformational analysis, synthesis and studies of bioactive compounds, including carbohydrate mimetics, asymmetric synthesis, and synthesis and studies of crown ethers and relative compounds. 

Therefore, in the first part of this section, intramolecular hydrogen transfers or intermolecular hydrogen transfers in preformed hydrogen bonded complexes in the solid state which are coupled only to minor heavy atom motions are discussed. H-transfers coupled to major heavy atom motions will then be treated in the second part they include pre-equilibria, hydrogen bond switches, conformational changes, solvent motions etc. 

Stimuli-responsive polymers consist of a class of smart materials that exhibit a physical response to changes in external conditions. Such stimuli include changes in pH, ionic strength, solvent polarity, and temperature, as well as mechanical force or electric fields. On the basis of their ability to switch conformations, stimuli-responsive polymers are being applied as sensors, actuators, and transducers (e.g., mechano-electrical or mechano-optical). Nanoporous membranes can be functionalized with stimuli-responsive polymers to modify their permeability, that is, to reversibly open and close the pores upon a given stimulus. ... 

There are also examples from our own lab of peptides designed to switch conformational state. One describes... 

A final example from our lab details how ZiCo, another de novo designed peptide, can switch conformational state upon binding zinc. In the absence of zinc, the peptide adopts a coiled-coil structure, but upon addition of zinc, absorption bands indicative of f-sheet are observed by FT-IR spectroscopy. Zinc binding is reversible and occurs in a 1 1 ratio. 

Fig. 10. Conformational flooding accelerates conformational transitions and makes them accessible for MD simulations. Top left snapshots of the protein backbone of BPTI during a 500 ps-MD simulation. Bottom left a projection of the conformational coordinates contributing most to the atomic motions shows that, on that MD time scale, the system remains in its initial configuration (CS 1). Top right Conformational flooding forces the system into new conformations after crossing high energy barriers (CS 2, CS 3,. . . ). Bottom right The projection visualizes the new conformations they remain stable, even when the applied flooding potentials (dashed contour lines) is switched off.

Long loop regions are often flexible and can frequently adopt several different conformations, making them "invisible" in x-ray structure determinations and undetermined in NMR studies. Such loops are frequently involved in the function of the protein and can switch from an "open" conformation, which allows access to the active site, to a "closed" conformation, which shields reactive groups in the active site from water. 

The subunits can switch between two distinct conformational states, R and T, which are in equilibrium. 

Figure 13.6 Schematic diagram of Go. from transducin with a bound GTP analog. The polypeptide chain is organized Into two domains a catalytic domain (light red) with a structure similar to Ras, and a helical domain (green) which is an Insert in the loop between al and P2. There are three switch regions (violet) that have different conformations in the different catalytic states of Go.. The GTP analog (brown) Is bound to the catalytic domain in a cleft between the two domains. (Adapted from J. Noel et al.. Nature 366 654-663, 1993.)...

Ga is activated by conformational changes of three switch regions... 

Figure 13.9 Conformational changes in the switch II and switch III regions of Gq.

Figure 13.10 Rearrangements of the hydrogen bond network between strands 1, 2, and 3 in the p sheet of Go. as a consequence of the switch from the GDP (blue) to the GTP (green) conformation. Strand P3 pulls away from pi and disrupts two hydrogen bonds in order to bring Gly 199 into contact with the y-phosphate of GTP. As a consequence new hydrogen bonds are formed between P2 and P3. (Adapted from D. Lambright et al.. Nature 369 621-628,...

Figure 13.15 Schematic diagram of the heterotrimeric Gap complex based on the crystal structure of the transducin molecule. The a suhunit is hlue with some of the a helices and (5 strands outlined. The switch regions of the catalytic domain of Gq are violet. The (5 suhunit is light red and the seven WD repeats are represented as seven orange propeller blades. The 7 subunit is yellow. The switch regions of Gq interact with the p subunit, thereby locking them into an inactive conformation that binds GDP but not GTP.

Binding to Gpy locks the flexible switch regions I and II of Ga into a conformation that firmly binds GDP but is nonproductive for GTP binding and hydrolysis. The replacement of GDP with GTP causes local but dramatic conformational changes to switch regions I and 11, as shown in the Go GTP-yS structure, which disrupt nearly all of the contacts between Gp. and Ga in the switch interface, thereby triggering release of Ga from Gpy (see Figures 13.10 and 13.11). 

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