All hitherto solved crystal structures of the catalytic (C) subunit of cAMP-dependent protein kinase can be classified into two groups, those with a closed and those with an open conformation of the ATP-binding lobe. The molecules with the closed conformation are all related by a crystallographic 2(1) axis that connects them into an infinite-chain motif. The motif has only one large contact region that involves many residues, several of them in the ATP-binding lobe, embedded in an extensive network of water molecules. The dominant feature of this region is the hydrophobic interaction between Trp196 and Arg133, Arg134. This motif has been found so far in three different crystal forms, two correspond to ternary enzyme-inhibitor-ATP complexes with mammalian and recombinant C, and one to a binary enzyme-inhibitor complex with recombinant C. The open conformation has been found in two closely related crystal structures, both of cubic symmetry, of the apoenzyme and a binary complex of the mammalian catalytic subunit. In this cubic structure of the binary complex, the hydrogen-bonded intramolecular contacts between Arg18 of the inhibitor and the ATP-binding lobe of the binary and ternary complexes of the recombinant enzyme are missing due to a strong hydrophobic intermolecular contact involving the diiodinated Tyr7. In solution, no crystal contacts prevent these hydrogen bonds involving Arg18 from forming so that it is likely that the binary complex with Tyr7 of the peptide inhibitor iodinated or not, can assume the closed conformation in solution. While the closed structure very likely represents a stable conformation in solution, there is no evidence to suggest that the open conformation represents a unique stable conformational state of the enzyme in solution.