Corresponding state hypothesis along the GTPase cycle in homologues

Marina Katava et al. have tracked the effect of substrate binding on the conformational flexibilities of two homologous GTPase domains of different stability contents by mimicking the catalytic cycle. The notable finding is that for the hyperthermophilic specie only at its high working temperature the release of entropy in the domain upon the hydrolysis of the GTP molecule matches that of the mesophilic domain at ambient condition. This was probed following several functional modes of the protein considered important for signalling propagation upon reaction as well as for the allosteric activation. It was also confirmed that the key region ensuring the flexibility for the conformational change upon catalysis (the switch I region) is also the weakest part in the mesophilic domain, confirming a sort of stability/function trade-off. You can enjoy the paper here.

A conserved structural element is a kinetic modulator of nucleotide exchange in the EF-Tu

A recent publication [1] reports that the P-loop, a conserved structural element in the catalytic domain of many different NTP-ases, might participate in modulating the nucleotide exchange rates for a broad class of NTP-ases.

The study was performed in detail on the EF-Tu protein, which catalyzes the GTP/GDP hydrolysis. Results show that the internal dynamics of the P-loop does not affect the nucleotide exchange rates, but rather P-loop forms a P-loop anchor via hydrogen bonds with another structural element of the protein, helix C. The P-loop anchor contributes to the activation entropy of the nucleotide exchange,  and consequently modulates the nucleotide-binding kinetics. 

Presently, two classes of P-anchors have been identified, depending on the nature of stabilization of the anchor, one class is hydrogen-bond stabilized, while the other is stabilized by the hydrophobic effect. The finding is consistent with the natural mechanism of the nucleotide exchange on the EF-Tu, where the nucleotide is exchanged upon the binding of another protein (EF-Ts) that disrupts the stability of the P-anchor, making the P-loop more flexible. The larger flexbility of the P-loop increases the entropic contribution to the activation free energy, resulting in faster nucleotide dissociation.

[1] Mercier E., Girodat D., Wieden H.-J., A conserved P-loop anchor limits the structural dynamics that mediate nucleotide dissociation in EF-Tu, JA  - Sci. Rep., 2015.