DEHYDRON: A PLAYER IN ENZYME CATALYSIS

Dehydrons are disruptive structural defects in proteins in the form of solvent-exposed backbone hydrogen bonds. Dehydrons create interfacial tension and promote their own dehydration, hence they play a central role as determinants of protein associations. Recently, Ariel Fernández has shown that dehydrons are also vital components of the enzymatic apparatus [Ariel Fernandez: COMMUNICATION: Chemical functionality of interfacial water enveloping nanoscale structural defects in proteins. Journal of Chemical Physics 140, 221102 (2014)]. The catalytic role of dehydrons is surely facilitated by their known physical attributes but hinges crucially on a newly found chemical functionality: dehydrons can also behave as a chemical base. To be more precise, dehydrons turn the interfacial water that envelops them into an effective proton acceptor. This chemical property coupled with the fact that dehydrons are ubiquitous at the catalytic site of protein enzymes becomes tale-telling, as Ariel Fernández has recently shown. The chemical role of dehydrons and their presence at catalytic site implies that dehydrons behave as quasi-reactants in biochemical reactions. This only means one thing: much of the mechanism in biological chemistry, especially those mysterious proton transferences between catalytic groups, vastly incompatible with their respective affinities, will have to be substantively revised.

Many reactions in enzyme catalysis require the activation of protein groups that perform or promote a nucleophilic attack leading to transesterification. In a recent communication, Ariel Fernández showed that interfacial water enveloping a dehydron acts as a chemical-base effector, enhancing the nucleophilicity of the adjacent active site. The results invite a revision of the purported elementary steps in biochemical reactions. On the other hand, novel biomolecular engineering is also likely to emerge as dehydron-based enzymatic effectors may be created or removed though site-directed mutation, tuning the local integrity of the protein structure.

In the context of enzymatic mechanisms the newly asserted chemical role of dehydrons complements exquisitely their previously established hydrophobicity or dehydration propensity. Thus, water enveloping a dehydron becomes a better leaving molecule (hydronium seeking full hydration) as the dehydron functionalizes the nucleophilic moiety of the enzyme, while the dehydration propensity of the dehydron induces the expulsion of the hydronium as it promotes the binding of the enzyme substrate. This migration of the dehydron-enveloping hydronium is both enthalpically and entropically favored, as the transference enables the fulfillment of hydration demands and confers higher translational freedom. The thermodynamic cost of transferring the proton from the catalytic group to the dehydron-functionalized water molecule is thus defrayed by the subsequent stabilization of the dehydron that results from its wrapping or shielding upon substrate association and by the free-energy decrease associated with migration of confined ionized water.

In this way, the dehydron functions as a catalytic device, a two-step component of the enzymatic apparatus. The implications of this discovery for biomolecular design, biochemical engineering and mechanistic biochemistry understood in its broadest sense are – we dare say – unfathomable. It is likely that entire chapters dealing with the mechanisms of biological chemistry will require revision to accommodate dehydron-based catalytic effectors, while novel molecular designs based on this concept herald a new era in enzyme catalysis.

Dehydrons stimulate enzyme catalysis – Yahoo News

AF’s Catalytic Dehydrons – The Wall Street Journal

Press Release: Ariel Fernandez Consultancy Discovers Structural Activator for Enzyme Catalysis

The dehydron is a key player in enzyme catalysis

Related Reading
Ariel Fernandez. Nonadaptive origins of interactome complexity. Nature 474, 502-505 (2011)

Ariel Fernandez

Ariel Fernandez Scientist/Consultant

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