Peptides contacts

Like the pentasaccharide, the octapeptide lies along the groove, roughly parallel to the Vh-Vl interface (Fig. 1A,B). One observes immediately that the peptide contacts some of the same areas of the binding site as the saccharide, but also extends into other areas of the site. The first four residues. Met Pl-Asp P2-Trp P3-Asn P4, adopt an extended conformation, and the last four residues. Met P5-His P6-Ala P7-Ala P8, form one turn of of-hefix. 

While these complex model heme proteins have a large potential for functionalization, an interesting approach that is very different has been taken by other workers in that the heme itself functions as the template in the formation of folded peptides. In these models peptide-peptide interactions are minimized and the driving force for folding appears to be the interactions between porphyrin and the hydrophobic faces of the amphiphiUc peptides. The amino acid sequences are too small to permit peptide-peptide contacts as they are separated by the tetrapyrrole residue. These peptide heme conjugates show well-re-solved NMR spectra and thus well-defined folds and the relationship between structure and function can probably be determined in great detail when functions have been demonstrated [22,23,77]. They are therefore important model systems that complement the more complex proteins described above. 

Woodland and slimy (Plethodon) salamanders are lung-less and lack an aquatic phase, reproducing in moist regions of the forest. They have evolved to employ large peptide contact pheromones, which are best understood in the Jordan s salamander and partially described in the Ocoee salamander.71... 

For TRAF recruitment, since each receptor peptide contacts one TRAP domain only, avidity is the only factor that contributes to enhanced affinity of TRAFs for activated receptors. Due to the lack of structural information on DD interactions, it is not known whether ligand-induced receptor recruitment of FADD and TRADD (Hsu et al, 1996b) is also purely driven by avidity or the intracellular DD of the receptors also form composite binding sites for FADD and TRADD upon receptor activation. In keeping with the latter scenario, a protein known as silencer of death domains (SODD) (Jiang et al, 1999) has been shown to associate with the intracellular DD of TNF-Rl and get released upon ligand stimulation to activate the receptor. 

The bound macrolides almost completely occlude the peptide exit tunnel, which explains the two distinctive characteristics of macrolide inhibition. Firstly, the reason that macrolides do not inhibit ribosomes that are already actively making protein is that the nascent peptide in the exit tunnel blocks access to the macrolide binding site. Secondly, the reason macrolides do not directly inhibit the peptidyl transferase reaction is that they bind near to, but not directly at, the active site. Only after a few peptide bonds are formed will the peptide contact the bound macrolide and be blocked from further elongation. As a result, short di-, tri- and tetra-peptides will accumulate. 

SH Bryant, LM Amzel. Coirectly folded proteins make twice as many hydrophobic contacts. Int J Peptide Protein Res 29 46-52, 1987. 

The Src SH2 domain typifies a large number of those characterized to date. The pTyr fits into a pocket on the opposite side of the central sheet to the pY-r3 pocket (Figure 13.27a). All known SH2 domains bind pTyr in essentially the same way, but some have a different pattern of contacts for the residues that follow. For example, in the Grb2 SH2 domain, a tryptophan side chain from the small sheet fills the pY-r3 pocket, and the bound peptide takes a different course, with important interactions to an asparagine at pY-r2. Screens of peptide libraries have detected the importance of this asparagine. The SH2 domain from PFC-yl contacts five mainly hydrophobic residues that follow pTyr. 

Figure 15.19 Schematic representation of the peptide-binding domain of a class I MHC protein. The al and a2 domains are viewed from the top of the molecule, showing the empty antigen-binding site as well as the surface that is contacted by a T-cell receptor. (Adapted from P.J. Bjdrkman et al.. Nature 329 506-512, 1987.)...

Andrew Braisted and J.A. Wells prepared phage containing Z domain helices 1 and 2 and restored Fc binding of this 38 residue minidomain in three iterative stages (see Figure 17.10). The truncated peptide was first randomized at four hydrophobic residues which contact helix 3 in the complete Z domain. The consensus sequence from this library maintained the wild-type residues lie 17 and Leu 23 while the hydrophobic residues Leu 20 and... 

The two peptides form a symmetrical dimer stabilized by four hydrogen bonds (red dashes) and hydrophobic contacts. The two monomers form a four-stranded, anti-parallel pleated sheet. 

Weak intramolecular interactions between sulfur or selenium and nitrogen are a recurrent phenomenon in large biomolecules. They may occur in the same residue or between neighbours of a peptide chain. The formation of four- or five-membered rings of the types 15.1 and 15.2, respectively, is most common. A feature that is unique to proteins is the participation of sulfur atoms in bifurcated N S N contacts. 

Fig. 12A, has a 10° libration. This gives a channel size which would be optimal for an ionic radius between that of Rb+ and Cs+. Therefore enhanced discrimination is not expected between Rb+ and Cs+, but the energy required to librate further inward to make contact with smaller ions in the series can be expected to enhance selectivity between these ions. Work is currently in progress to calculate the change in channel energy as a function of libration angle or of the equivalent, the effective channel radius S6). The implications of a peptide libration mechanism for enhancing ion selectivity can also be pursued experimentally as outlined below. 

Different enzymes have different specificities. Some, such as amylase, are specific for a single substrate, but others operate on a range of substrates. Papain, for instance, a globular protein of 212 amino acids isolated from papaya fruit, catalyzes the hydrolysis of many kinds of peptide bonds. In fact, it s this ability to hydrolyze peptide bonds that makes papain useful as a meat tenderizer and a cleaner for contact lenses. 

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