Neutral trehalase 1 (Nth1) from Saccharomyces cerevisiae
catalyzes disaccharide trehalose hydrolysis and helps yeast to
survive adverse conditions, such as heat shock, starvation or
oxidative stress. 14-3-3 proteins, master regulators of hundreds
of partner proteins, participate in many key cellular processes.
Nth1 is activated by phosphorylation followed by 14-3-3 protein
(Bmh) binding. The activation mechanism is also potentiated by
Ca2+ binding within the EF-hand-like motif. This review
summarizes the current knowledge about trehalases and the
molecular and structural basis of Nth1 activation. The crystal
structure of fully active Nth1 bound to 14-3-3 protein provided
the first high-resolution view of a trehalase from a eukaryotic
organism and showed 14-3-3 proteins as structural modulators
and allosteric effectors of multi-domain binding partners.
PI4K IIα is a critical enzyme for the maintenance of Golgi and is also known to function in the synaptic vesicles. The product of its catalytical function, phosphatidylinositol 4-phosphate (PI4P), is an important lipid molecule because it is a hallmark of the Golgi and TGN, is directly recognized by many proteins and also serves as a precursor molecule for synthesis of higher phosphoinositides. Here, we report crystal structures of PI4K IIα
enzyme in the apo-state and inhibited by calcium. The apo-
structure reveals a surprising rigidity of the active site residues important for catalytic activity. The structure of calcium inhibited kinase reveals how calcium locks ATP in the active site.