Peptide residues, interaction with

Conversely, the peptide has interactions with the top and roof of the active site, and in fact binding causes some opening of the roof the side chain of Ala 3 and the backbone of N-MePhe 2 both contact Trp 97, and residues 2, 4 and 5 contact Asp 316 and Pro 317, which form part of the roof . The side chain of Asp 316 is directed away from the active site in order to accommodate the bound peptide, and the backbone of the loop containing residues 316-317 moves also. 

Dark-shaded residues interact with calmodulin s C-terminal domain. Light-shaded residues interact with calmodulin s N-terminal domain. For CaMKK peptides, the reverse is true. 

In addition to finding small organic molecules that bind to a protein, covalent capture methods can identify peptides that interact with proteins. Kohda and colleagues used this approach to study the mitochondrial protein Tom20, an import receptor that recognizes an epitope on proteins targeted for the mitochondria.1301 Previous work had characterized this epitope as a five-residue peptide that assumes an amphiphilic helical conformation, and coarse sequence preferences had been worked out. However, Tom20 has both low affinity... 

Figure 14.22 Structure of the SH2 domain. The domain is shown bound to a phosphotyrosine-contalning peptide. Notice at the top that the negatively charged phosphotyrosine residue interacts with two Arg residues that are conserved in essentially all SH2 domains. [Drawn from ISPS.pdb.]...

In addition, the acetylated lysine residues interact with a specific acetyilysine-binding domain that is present in many proteins that regulate eukaryotic transcription. This domain, termed a bromodomain, comprises approximately 110 amino acids that form a four-helix bundle containing a peptide-binding site at one end (Figure 31.31). 

Fig. 6. Mode of peptide binding to the GroEL apical domain. Residues 197-335 of the apical domain are shown as a ribbon diagram, with three binding peptides (black) overlaid. The hydrophobic binding residues identified by mutagenesis (Fenton et al., 1994) are shown in light-colored, space-filling format. Also shown are side chains of the binding peptides that interact with the apical domain.

The structural basis for recognition of protein substrates is not yet clear. However, structures of PAD4 in complex with A -benzoyl-L-arginine amide and peptides from histones H3 and H4 that are known to he citrullinated have provided clues as to how PAD4 hinds and recognizes small molecule substrates. As with ADI and DDAH, the arginine residue of the substrate binds at the center of the propeller of the catalytic domain, and the conserved core residues interact with the guanidine side chain. ... 

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