However, we note that if protein sites are strongly coupled, which is often the case, any conformational change will affect the active site conformation.
Molecular dynamics simulations suggest that the mutations alter the conformational landscape of the enzyme, favoring a more open active site conformation that facilitates the reactivity of the larger substrate.
On the other hand, the binding of Mg-ATP to one subunit would lead to overall enzyme conformational changes, thus inducing the stabilization of the open active site conformation in the next subunits, and increasing their affinity for Mg-ATP.
These data suggested that surface acidic residue Glu226 might play role in proper maintenance of active site conformation.
Therefore, we propose that this active site conformation is the biologically relevant conformation and can be used for the future structure-based drug design studies selectively targeting IN.
Superimposition of the loop with reactive sites of other canonical protease inhibitors shows that reactive site conformation of AmFPI-1 is similar to them.
Thus, a novel binding site conformation has been identified in a region where previous complex structures suggested only low adaptability of the binding pocket.
Some surfactants may cause alterations in the interfacial properties or changes of the lipase active site conformation preventing the binding of lipase to substrate, resulting in enzyme inactivation (Khoramnia et al. 2011).
Thus, aromatase inhibitors were also used more recently to probe and understand the active site conformation of the enzyme and its modelization was obtained from comparisons with bacterial-related cytochromes.
The transition state analogue 2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA), which inhibits sialidases but is a poor inhibitor of trans-sialidase, was used to probe the active site conformation of mutant enzymes.
More detailed investigation will be implemented during the year of 2010 to 2013 including works of site conformation, characterization prior to performing a pilot test with injection depth down to 2500 ∼3000 m.
