Orchestrating function: Concerted dynamics, allostery, and catalysis in protein tyrosine phosphatases

Protein tyrosine phosphatases (PTPs) are a family of enzymes that play critical roles in intracellular signaling and regulation. PTPs are conformationally dynamic, exhibiting motions of catalytic loops and additional regions of the structurally conserved catalytic domain. However, many questions remain about how dynamics contribute to catalysis and allostery in PTPs, how these behaviors vary among evolutionarily divergent PTP family members, and how mutations and ligands reshape dynamics to modulate PTP function. Recently, our understanding in these areas has expanded significantly, thanks to novel applications of existing methods and emergence of new approaches in structural biology and biophysics. Here we review exciting advances in this realm from the last few years. We organize our commentary both by experimental and computational methodologies, including solution techniques, avant-garde crystallography, molecular dynamics simulations, and bioinformatics, and also by scientific focus, including regulatory mechanisms, mutations and protein engineering, and small-molecule ligands such as allosteric modulators.