Salt bridges, Glu-Lys

Baldwin and co-workers [4] have made a pioneering contribution in this area. They demonstrated that short (11-15 residues) alanine-rich peptides (such as 1), having several glu-lys salt bridges adopt a stable monomeric a-helix structure in solution. 

Marqusee S, Baldwin RE (1987) Helix stabilization by Glu-...Lys + salt bridges in short peptides of de novo design. Proc Nad Acad Sci U S A 84 8898-8902... 

EIectrosta.tlcs. Electrostatic interactions, such as salt bridges, result from the electrostatic attraction that occurs between oppositely charged molecules. These usually involve a single cation, eg, the side chain of Lys or Arg, or the amino terminus, etc, interacting with a single anion, eg, the side chain of Glu or Asp, or the carboxyl terminus, etc. This attractive force is iaversely proportional to the distance between the charges and the dielectric constant of the solvent, as described by Coulomb s law. 

The amino acid sequence of our first aPNA (which we termed backbone 1 or bl) was designed based on this amphipathic hehx sequence (Fig. 5.3 B). Specifically, this aPNA backbone included hydrophobic amino acids (Ala and Aib), internal salt bridges (Glu-(aa)3-Lys-(aa)3-Glu), a macrodipole (Asp-(aa)i5-Lys), and an N-ace-tyl cap to favor a-helix formation. The C-termini of these aPNA modules end in a carboxamide function to preclude any potential intramolecular end effects. Each aPNA module incorporates five nucleobases for Watson-Crick base pairing to a target nucleic acid sequence. 

The polar, charged residues Asp, Glu, Lys, Arg and, in its protonated form, His, will often be found at the surface of proteins, where they may not only interact with the polar layers of ordered water molecules surrounding the protein, but may also participate in hydrogen bonds and salt bridges with other polar charged residues. 

His HC3j8, and it has Gly rather than Lys in position HCljS to prevent anchoring of the C terminus in R structure (Table I). On the other hand, it has a Lys at F6/3, one turn of the tt helix away from the Glu FG1)8 and capable of competing with His HC3/8 for the essential salt bridge with that Glu (Figs. 4 and 5). This competition may weaken its alkaline Bohr effect compared to that of carp. 

Figure 19.8 (a) Structure of native CI2 plus four simulated transition states for unfolding. [From A. J. Li and V. Daggett, Proc. Natl. Acad. Sci. USA 91,10430 (1994) A. J. Li and V. Daggett, l Molec. Biol. 257,412 (1996)). (b) Residues Lys-2, Glu-7, and Asp-23 form a triple salt bridge in the native structure (right) that is broken in the simulated transition states for the unfolding (left). 

Thus, negatively charged moieties in proteins (such as the carboxylate side chains of Asp and Glu residues) frequently interact with positively charged side chains of Lys, Arg, or His residues. These electrostatic interactions often result in the formation of salt bridges, in which there is some degree of hydrogen bonding in addition to the electrostatic attraction, as illustrated in Fig. 4-3. 

Structurally, the interface between the two halves of the molecule is held together by both hydrophobic and salt bridge interactions. Among these residues there are potential salt bridges between Lys-205 and Glu-465, Asp-187 and both Lys-432 and Arg-521, Arg-218 and Asp-451, and Lys-190 and Glu-425, which should be more clearly defined in a higher resolution crystal structure. Hydrophobic interactions that associated lA, IB, and IIA, with HB, IIIA, and IIIB include a major interdomain cluster involving Phe-206, Leu-481, Ala-482, Trp-214, Leu-347, Val-344, Val-343, Leu-331, Ala-217, and Tyr-452. 

Succinyl-L-tryptophan-L-tryptophan (STT, 8) and p-bromobenzyl-oxyacetic acid (BBA, 9) also bind to deoxyhemoglobin at several sites. In the case of STT, four different sites are involved. The major portion of binding in the case comes from hydrophobic contacts in which 21 molecules of water are displaced. Each STT is bound to one a. subunit by three hydrogen bonds and several van der Waals interactions (Figure 18). STT binds to the protein with a Kd of 3.0 mM. BBA is held in place by a salt bridge between its carboxylate and Lys-40. There are also van der Waals contacts between its bromine and the aliphatic protion of the side chain of Glu-30 (Figure 19). 

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