NAD-/FAD-binding residue templates were then constructed by identifying binding residues through the ligand-binding database BioLiP.
The key residues of PKBα interacting with the allosteric inhibitor were further discussed by analyzing the different interaction modes of these three inhibitors binding to PKBα and by calculating binding free energy contributions of corresponding residues around the binding pocket.
It takes averagely 1 3 minutes for binding sites detection, and the potential binding sites can be interactively viewed and downloaded in PDB files for off-line analysis, which includes the binding pocket surface, the residues around the site, and key features of the pharmacophore model derived from the site.
We have analyzed the preference of neighboring residues around the binding sites in protein-RNA complexes using the occurrence of dipeptides adjacent to the binding sites and their respective occurrences in the whole protein.
Alanine scanning of the active-site residues shows that both the catalytic lysine and the residues around the binding pocket for the substrate naphthyl group make critical contributions to catalysis.
However, a study of the residues at the active site region located in the C-terminal domain and the degree of conservation around the metal ion shows that metal binding residues (three histidines and a glutamate) and nearby residues tryptophan, methionine, tyrosine, phenylalanine and arginine are conserved while serine is conservatively substituted by threonine (figure not shown).
The metal binding residues are not conserved.
Here, the metal binding residues are contributed by two subunits.
The residues around the Ca2+-binding site in TbMCA2 are also involved in salt-bridge formation, with the N-terminal region, and it is intriguing to assume that Ca2+ could disrupt interactions of the inhibitory regions, producing (or allowing for) the conformational change required for substrate access.
(A) The first four residues (BBR, backbone binding residues) of a TALE repeat are responsible for DNA backbone binding.
