Protein kinase G (PKG) is an essential regulator of eukaryotic cGMP-dependent intracellular signaling, controlling pathways that are often distinct from those regulated by cAMP. Specifically, the C-terminal cyclic-nucleotide-binding domain (CNB-B) of PKG has emerged as a critical module to control allostery and cGMP-selectivity in PKG. While key contributions to the cGMP- versus-cAMP selectivity of CNB-B were previously assessed, only limited knowledge is currently available on how cyclic nucleotide binding rewires the network of hydrogen bonds in CNB-B, and how such rewiring contributes to allostery and cGMP selectivity. To address this gap, we extend the comparative analysis of apo, cAMP- and cGMP-bound CNB-B to H/D fractionation factors (FFs), which are well-suited for assessing backbone hydrogen-bond strength within proteins. Apo- versus-bound comparisons inform on perturbations arising from both binding and allostery, while cGMP- versus cAMP-bound comparisons inform on perturbations that are purely allosteric. Comparative FF analyses of the bound states revealed mixed patterns of hydrogen-bond strengthening and weakening, pointing to inherent frustration, whereby not all hydrogen bonds can be simultaneously stabilized. Interestingly, contrary to expectations, these patterns include a weakening of hydrogen bonds not only within critical recognition and allosteric elements of CNB-B, but also within elements known to undergo rigid-body movement upon cyclic nucleotide binding. These results suggest that frustration may contribute to reversibility of allosteric conformational shifts by avoiding over-rigidification that may otherwise trap CNB-B in its active state. Considering that PKG CNB-B serves as a prototype for allosteric conformational switches, similar concepts may be applicable to allosteric domains in general.