RESUMEN
In this work, we combine experiments and molecular simulations to unveil the hidden allosteric propensity of a thermophilic malate dehydrogenase protein (MDH). We provide evidence that, at its working temperature, the nonallosteric MDH takes a compact structure because of internal dewetting and reorganizes the active state toward functional conformations similar to its homologous allosteric LDHs. Moreover, a single-point mutation confers on the MDH a cooperative behavior that mimics an allosteric LDH. Our work not only demonstrates that thermophilic MDHs use temperature as an external parameter to regulate its functionality in a similar way allosteric LDHs use substrates/cofactors binding but also shows that the scaffold of MDHs possesses an intrinsic and hidden allosteric potentiality.