Through extensive mutagenesis trial-and-error efforts, a stable, homodimeric construct of the catalytic core domain of the HIV1 integrase enzyme has been generated. Although under conditions that closely resemble the physiological environment the enzyme rapidly samples different conformational states, leading to extensive line broadening and disappearance of NMR signals, we have found conditions that include high Mg2+ concentrations (40 mM) where the equilibrium is shifted to what appear to be one major and one minor state, that differ from one another in the structure of the C-terminal helix. The NMR chemical shifts are found to corroborate structures observed in crystals, and confirm prior studies suggesting that the α4 helix extends toward the active site. The strong improvement in spectral quality with Mg2+ concentration suggests a structural transition not only near the active site residues but also throughout the entire molecule as IN binds Mg2+. In particular, the stability of the core domain is linked to the conformation of its C-terminal helix, which has implications for relative domain orientation in the full length enzyme. 15N relaxation experiments further show that, while conformationally flexible, the catalytic loop of IN is not fully disordered in the absence of DNA. Indeed, automated chemical shift-based modeling of the active site loop reveals several stable clusters which show striking similarity to a recent crystal structure of prototype foamy virus (PFV) IN bound to DNA.