Innovative pharmaceutics and biotechnology paradigms translating advances in chemistry
From a structural perspective, dehydrons are ubiquitous at catalytic sites in protein enzymes. As it turns out, this localization is vital to establish their role as promoters of enzymatic activity. As Ariel Fernandez has recently shown , dehydrons not only induce protein associations but also act as a chemical base. This dual role makes them key players in enzyme catalysis: the dehydron is a catalytic effector, enhancing the nucleophilicity of vicinal enzymatically competent groups in trans-esterification reactions. This finding invites a thorough mechanistic revision of biochemical reactions and has broad implications in biomolecular design, as catalytic effectors may be engineered or remove almost a la carte by creating or removing structural defects in protein enzymes.
What is a dehydronic enzyme? This term coined by Ariel Fernandez refers to a protein enzyme that uses dehydrons as internal co-catalysts to promote trans-esterification reactions through an activation of the nucleophilic agent. More precisely, dehydronic enzymes harness the proton-acceptor role of dehydrons vicinal to the catalytic site to induce and stabilize the polarized state of the latter which is thereafter enabled to attack an ester linkage in the enzyme substrate. Dehydrons also enable proton transference within the catalytic triads of proteases and other enzymes that require cooperation among catalytically competent side chains. As the reader may surmise, the engineering and design possibilities stemming from this finding are virtually infinite, as side chains may be functionalized or silenced by respectively creating or removing vicinal dehydrons through a tuning of the chemical composition of the protein chain.
As noted by Ariel Fernandez , the workings of the dehydronic enzyme actually harnesses on the dual role of the dehydron as a chemical base and a promoter of protein association. While the catalytic site is partially filled with water, the dehydron prepares or activates the nucleophile. On the other hand, once catalytic preparation is complete and the hydronium is concomitantly created, the enzyme has a better leaving group in keeping with the dehydron propensity to promote its own dehydration. The dehydron thus acts as a two-step catalytic engine realizing a favorable thermodynamic cycle.