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We varied the Ag NW radii rAg and air gap width d and studied the corresponding variations in the modal characteristics of the hybrid modes for substrate thicknesses t=5 or 500 nm.
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This model might be called a "middle-first" entry mode for substrate, in contrast to historical discussions couched in terms of "head-first" and "tail-first" entry through a localized site.
These interactions allow for two distinct modes of substrate binding.
Understanding the structural biology of protein kinases in detail, including their commonalities, differences and modes of substrate interaction, is necessary for designing high quality inhibitors that will be of true use for cell biology and disease therapy.
By combining all crystal structures solved here, a comprehensive binding mode for a substrate is proposed.
The simplest model to account for the Y47F and H49A data involves at least two modes of substrate docking into the active site.
These observations suggest that nonproductive modes of substrate binding are possible and may contribute to the low rates of turnover measured for cADO.
In spite of the structural plasticity of CYP3A4, we have been able to use MD simulations to identify plausible productive and nonproductive binding modes for one or more substrate molecules in the substrate-binding pocket of the enzyme.
Therefore, present ligand is also a model system for interpretation of the possible mode of substrate binding and catalytic action.
Comparison of all variant activities on each substrate indicated different binding modes for the three aromatic substrates, supported by computational docking.
We hypothesize that this might be due in part to the altered mode of substrate selection that we have observed for Hsp104A503V.
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