Several key residues within the nucleotide binding pocket that interact with the nucleotide base were mutated in the murine isoform of PKA (L49A, V57A, L104A, M120A, Y122A, L173A, T183A and F327A) [9].
In particular, compounds with modifications that extend the R1 position of the phenyl group with hydrophobic motifs might enable compound analogues to reach deeper into the EBNA1-binding pocket that interacts with residue Pro535 and Leu536 of EBNA1.
The HSP90 homologue gp96 also contains a binding pocket and, like HSP90, it is an open binding pocket that should allow peptides of any length to interact with it, though the presence of a disulphide bond in this domain may also affect peptide binding [ 75].
Recent successes in identifying potent NNIs are reviewed with an emphasis on the recent trend of utilizing a computer model of HIV RT to identify space in the NNI binding pocket that can be exploited by carefully chosen functional groups predicted to interact favorably with binding pocket residues.
Computational docking studies and site-directed mutagenesis analysis identified key residues within PXR's ligand-binding pocket that interact with BPA.
Alternatively AHLs with greater lipophilicity will interact more readily with any hydrophobic binding pockets that exist within receptor systems (i.e. either in a membrane or in a soluble protein).
Lys217, typically an arginine residue in other DHPS enzymes, can potentially interact with the carboxyl group of pABA or contribute to the anion-binding pocket that engages the β-phosphate of the DHPPP substrate.
It may be that multiple domains of PfEMP1 contribute to a single binding pocket, that multiple domains interact with different receptors, or that antibodies to other domains interfere with DBL1α-receptor interactions by steric hindrance or by disrupting interactions which stabilize higher-order organization of the protein.
The HBGA binding interface of BV is composed of a conserved central binding pocket (CBP) that interacts with the β-galactose of the precursor, and a well-developed Le epitope-binding site formed by five amino acids, including three consecutive residues from the long P-loop and one from the S-loop of the P1 subdomain, a feature that was not seen in the other GI NoVs.
In comparison with the S5 S1 pockets, the prime-side binding pockets, which interact with the P′ residues downstream of the cleavage junction, are less well defined.
