Distant residues

The native conformation of proteins is stabilized by a number of different interactions. Among these, only the disulfide bonds (B) represent covalent bonds. Hydrogen bonds, which can form inside secondary structures, as well as between more distant residues, are involved in all proteins (see p. 6). Many proteins are also stabilized by complex formation with metal ions (see pp. 76, 342, and 378, for example). The hydrophobic effect is particularly important for protein stability. In globular proteins, most hydrophobic amino acid residues are arranged in the interior of the structure in the native conformation, while the polar amino acids are mainly found on the surface (see pp. 28, 76). 

Chirality is a pervasive property of an object, which means that in theory, a single remote asymmetric center in a macromolecule is enough to make the entire molecule chiral and, in principle, even the more distant residue could sense the asymmetry induced by the stereogenic center. On the contrary, experiences maturated by synthetic chemists in the construction of molecular species for enantioselective recognition speak for the necessity of placing the asymmetric units in close contact to allow chiral sensing and discrimination. The latter, in fact, arises from attractive forces and steric interactions that require close contact between the counterparts. On the contrary, magnetic asymmetry is not a direct consequence of weak interactions, but is more a property of the space which surrounds a chiral object. 

Figure 21.4 Cartoon picture of the PAMO crystal structure. The FAD co-factor is shown in sticks in the center together with the active site R337. Residues that are <15 A from the isoalloxazin moiety of the FAD co-factor are shown in dark gray balls, while more distant residues are represented as light gray balls.

Figure 8.7. Active Sites May Include Distant Residues. (A) Ribbon diagram of the enzyme lysozyme with several...

Figure 8.7 Active sites may include distant residues. (A) Ribbon diagram of the enzyme lysozyme with several components of the active site shown in color. (B) A schematic representation of the primary structure of lysozyme shows that the active site is composed of residues that come from different parts of the polypeptide chain, [Drawn from 6LYZ.pdb.]...

NMR Spectroscopy The three dimensional structures of small proteins containing about as many as 200 amino acids can be studied with nuclear magnetic resonance (NMR) spectroscopy. In this technique, a concentrated protein solution Is placed in a magnetic field and the effects of different radio frequencies on the spin of different atoms are measured. The behavior of any atom Is Influenced by neighboring atoms In adjacent residues, with closely spaced residues being more perturbed than distant residues. From the magnitude of the effect, the distances between residues can be calculated these distances are then used to generate a model of the three-dimensional structure of the protein. 

FIGURE 8.7 Active sites may include distant residues. (A) Ribbon... 

The secondary structure consists of the local spatial arrangement of the polypeptide chain into repeating structures stabilised by hydrogen bonds, i.e. a-helices and P-sheets. In a-helices, hydrogen bonds are shared by amino acid residues close to each other in the primary sequence of the protein whereas in p-sheets, they involved distant residues. In addition proteins exhibit local non-repeating structures, i.e. turns. 

Tertiary structure refers to the folding of the protein into a characteristic shape, which is stabilized by attractive forces between more distant residues ... 

We have investigated the relative contribution of distant residues through the salt dependence of the proton uptake in various pH regions. The salt dependence is strong near neutral pH, but is absent at alkaline pH and much less marked at acid pH. We suggest that this reflects the involvement of amino acid residues of varying exposure or accessibility to screening by counter ions. The observed dependence may explain some of the discrepancies in earlier measurements of the stoichiometiy of proton uptake after the first flash [6-8]. 

Acid conditions. The effect of salts on the relative amplitude of the first flash-induced proton uptake at acid pH was intermediate between neutral and alkaline conditions, and could not be eliminated (Fig. 5). At pH 5.6, the value of the ratio H+(2)/H+(l) did not exceed 2.5, even at high CaCl2 concentration. This indicates that it is attributable to both easily screened, and probably distant, residues, and to less accessible residues, presumably close to Qb-... 

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