The conformation of the second extracellular loop, which often constitutes the top of the ligand binding site, is, however, quite different in the two structures.
We noticed that the vast majority of mutations affecting the PH domain involved solvent-exposed residues within two adjacent regions (i.e., residues 424 436 and 473 493) that do not overlap spatially with the PIP2-binding site, which is constituted by residues Lys456, Arg459, Lys472, and Arg489 [Zheng et al., 1997].
Otherwise, this binding site is regarded as an incorrectly predicted binding site.
Thus, the conformational states of the side chains constituting the DS binding site are unlikely to drastically change the outcome of the CVLS study.
The Cu-binding site in PETE2 is constituted of amino acids His, Cys and His.
Two of them (HEAT repeats 9 13 and 14 18), which constitute the substrate binding site, are rigid elements that rotate relative to each other about a flexible hinge.
Although sequence identities between the CYP51 orthologues in eukaryotic species are low (about 25%), amino acids constituting the substrate binding sites are far more conserved.
Potential binding sites were elucidated by docking.
These binding sites are highly charged.
Our identification and experimental validation of the c-Jun and Jun-D-binding sites, the discovery of their mitochondrial localization in human cells, and the finding that these binding sites are negatively selected constitute the first solid evidence for the functional importance of these sites.
