Hydrophobic patches

Lesk and Chothia did find, however, that there is a striking preferential conservation of the hydrophobic character of the amino acids at the 59 buried positions, but that no such conservation occurs at positions exposed on the surface of the molecule. With a few exceptions on the surface, hydrophobic residues have replaced hydrophilic ones and vice versa. However, the case of sickle-cell hemoglobin, which is described below, shows that a charge balance must be preserved to avoid hydrophobic patches on the surface. In summary, the evolutionary divergence of these nine globins has been constrained primarily by an almost absolute conservation of the hydro-phobicity of the residues buried in the helix-to-helix and helix-to-heme contacts. 

Figure 3.13 The hemoglobin molecule is built up of four polypeptide chains two a chains and two (3 chains. Compare this with Figure 1.1 and note that for purposes of clarity parts of the a chains are not shown here. Each chain has a three-dimensional structure similar to that of myoglobin the globin fold. In sicklecell hemoglobin Glu 6 in the (3 chain is mutated to Val, thereby creating a hydrophobic patch on the surface of the molecule. The structure of hemoglobin was determined in 1968 to 2.8 A resolution in the laboratory of Max Perutz at the MRC Laboratory of Molecular Biology, Cambridge, UK.

Figure 3.14 Sickle-cell hemoglobin molecules polymerize due to the hydrophobic patch introduced by the mutation Glu 6 to Val in the P chain. The diagram (a) illustrates how this hydrophobic patch (green interacts with a hydrophobic pocket (red) in a second hemoglobin molecule, whose hydrophobic patch interacts with the pocket in a third molecule, and so on. Electron micrographs of sickle-cell hemoglobin fibers are shown in cross-section in (b) and along the fibers in (c). [(b) and (c) from J.T. Finch et al., Proc. Natl. Acad. Set. USA 70 718-722, 1973.)...

The thioredoxin domain (see Figure 2.7) has a central (3 sheet surrounded by a helices. The active part of the molecule is a Pa(3 unit comprising p strands 2 and 3 joined by a helix 2. The redox-active disulfide bridge is at the amino end of this a helix and is formed by a Cys-X-X-Cys motif where X is any residue in DsbA, in thioredoxin, and in other members of this family of redox-active proteins. The a-helical domain of DsbA is positioned so that this disulfide bridge is at the center of a relatively extensive hydrophobic protein surface. Since disulfide bonds in proteins are usually buried in a hydrophobic environment, this hydrophobic surface in DsbA could provide an interaction area for exposed hydrophobic patches on partially folded protein substrates. 

Before protein molecules attain their native folded state they may expose hydrophobic patches to the solvent. Isolated purified proteins will aggregate during folding even at relatively low protein concentrations. Inside cells, where there are high concentrations of many different proteins, aggregation could therefore occur during the folding process. This is prevented by... 

Structural information about the oxygenases provided limited insight into the mechanism (Schmidt et al. 2006). The crystallized enzyme from Synechocystis sp. PCC6803 is membrane associated and the interaction with the membrane is believed to be mediated by a nonpolar patch on the surface of the enzyme. This hydrophobic patch is thought to provide the necessary access of the protein to the membrane-bound carotenoids. Following withdrawal from the membrane, the substrate moves through the hydrophobic tunnel toward the metal center. The substrate orients the... 

SPECIFICITY in the association of two proteins or a protein and a small molecule results from the requirement that the two interacting molecules must be complementary—complementary in charge, hydrogen bonding, and hydrophobic patches as well as shape. If any of the possible interactions are not satisfied, the strength of the interaction suffers. 

The LOCK AND KEY model for enzyme specificity uses complementarity between the enzyme active site (the lock) and the substrate (the key). Simply, the substrate must fit correctly into the active site—it must be the right size and shape, have charges in the correct place, have the right hydrogen-bond donors and acceptors, and have just the right hydrophobic patches. 

Stability Sugar side chains can potentially stabilize a glycoprotein in a number of ways, including enhancing its solubility, shielding hydrophobic patches on its surface, protection from proteolysis and by direct participation in intrachain stabilizing interactions... 

CSPs has, overall, a hydrophobic character (very similar to RP phases with C4-C8 ligands) which stems from contributions of the chiral selectors itself and (capped) linker groups (only a portion of the linkers are utilized for selector attachment) which constitutes a kind of hydrophobic basic layer on the support surface. Hence under typical RP-conditions, hydrophobic interactions between lipophilic residues of the solute and hydrophobic patches of the sorbent may be active and thus a reversed-phase like partition mechanism may be superimposed upon the primary ion-exchange process k = A rp -I- A ix). This A Rp-retention contribution may be especially important for eluents with high aqueous content. 

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