Ariel Fernandez Consultancy Discovers a Structural Activator for Enzyme Catalysis

HOUSTON - July 3, 2014 - PRLog -- Ariel Fernandez Consultancy (http://www.arielfernandez.net/) serves the Pharmaceutical and Biotechnology industries by providing thought leadership rooted in fundamental discoveries that can broaden their technological base. In line with this goal, recent research at Ariel Fernandez Consultancy revealed that a structural defect in natural proteins known as dehydron plays an important and previously unreported role in enzyme catalysis. The newly discovered structure-based effector of protein function has broad implications for biomedical engineering, enzyme optimization and pharmaceutical design.

Dehydrons are structural defects in proteins discovered over a decade ago by Ariel Fernandez, Ridgway Scott and Harold Scheraga (Ariel Fernandez (2010) Transformative Concepts for Drug Design: Target Wrapping, ISBN 978-3642117916, Springer, Berlin). Strikingly, it has been recently shown that dehydrons are also important components of the enzymatic apparatus of proteins (Ariel Fernandez (2014) Journal of Chemical Physics 140, 221102, Communication, http://scitation.aip.org/content/aip/journal/jcp/140/22/1...). The newly discovered catalytic role of dehydrons is enabled by their known physical attributes but hinges crucially on their recently established chemical functionality: a dehydron behaves as a powerful chemical base. This chemical property has been recently inferred by the rigorous theoretical and computational methods of molecular biophysics and by examining databases of protein structure.

As recently shown at Ariel Fernandez Consultancy (http://www.arielfernandez.net/dehydronic-enzymes.html), when the newly found chemical function is coupled with the observation that dehydrons are ubiquitous at the catalytic sites of protein enzymes, a striking picture with manifold biotechnological implications emerges: dehydrons serve as key structural activators of enzyme catalysis and hence become novel target features guiding enzyme and drug (enzyme inhibitor) design.

Since dehydrons are now being shown to behave as bio-reactants, actively participating in catalytic chemical steps, much of the mechanism in biological chemistry will have to be substantively revised, while a paradigmatic concept for biomedical design emerges. Thus, novel bio-engineering tools for molecular optimization will be implemented at Ariel Fernandez Consultancy (http://www.arielfernandez.net/) as dehydron-based enzymatic effectors are created or removed though site-directed mutation, fine-tuning the local integrity of the underlying protein structures.

The finding now makes it possible to activate or silence a catalytic site in a protein enzyme by respectively creating or annihilating a nearby dehydron through an engineered change in the chemical composition of the protein. On the other hand, novel and selective drug-based inhibitors of enzymatic activity will emerge as dehydrons are targeted through engineered protein-drug associations. Thus, drugs may deactivate enzymatic sites by “correcting” structural defects in proteins upon association with the latter.

The discovery has broad implications for biomedical engineering and biochemical optimization. Numerous “established” biochemical reactions will require revision to include dehydron-based catalytic activators, while novel molecular designs based on this concept are likely to herald a new era in the optimization of enzyme catalysts and pharmaceuticals.