Differences in the overall strength of the decay in fluorescence intensity indicate slightly different binding geometry for the four GAGs.
We show that, while each of the compounds binds with the inositol headgroup inserting into the proposed active site of the PTEN phosphatase domain, hydrogen bonding restrictions lead to distinct binding geometries for ligand pairs of opposite chirality.
The binding geometry implicates Arg464, a hitherto unheralded residue, as being important for D6 recognition.
This binding geometry was confirmed by a subsequent X-ray crystallographic study of alkaline phosphatase.
The development of docking software that is able to accurately predict binding geometry and binding energy represents a great challenge in computational chemistry [68, 71 73].
Therefore, while IAA does bind strongly to AFB5, selection for more than a single binding geometry suggests that there might be additional endogenous ligands still to be described.
In addition, His459, which is strictly conserved among the oxidases, probably carries a hydrogen atom at Nε2, which would make it a very unlikely general base for any other potential substrate with a binding geometry more similar to the oxidases.
This results in a binding geometry which agrees well with results from previous docking studies (14).
Including the entropy term also preserved the successful prediction of the binding geometry compared to the crystallographic structure for the rest of the small molecule DNA systems.
Borbulevych, O. Y., Piepenbrink, K. H. & Baker, B. M. Conformational melding permits a conserved binding geometry in TCR recognition of foreign and self molecular mimics.
