Nanosecond ligand exchange dynamics at metal sites within proteins is essential in catalysis, metal ion transport, and regulatory metallobiochemistry. Herein we present direct observation of the exchange dynamics of water at a Cd2+ binding site within two de novo designed metalloprotein constructs using perturbed angular correlation (PAC) of gamma-rays and Cd-113 NMR spectroscopy. The residence time of the Cd2+-bound water molecule is tens of nanoseconds at 20 degrees C in both proteins. This constitutes the first direct experimental observation of the residence time of Cd2+ coordinated water in any system, including the simple aqua ion. A Leu to Ala amino acid substitution similar to 10 angstrom from the Cd2+ site affects both the equilibrium constant and the residence time of water, while, surprisingly, the metal site structure, as probed by PAC spectroscopy, remains essentially unaltered. This implies that remote mutations may affect metal site dynamics, even when structure is conserved.