CHAPS [3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulfonate] is a non-denaturing detergent widely used for protein solubilization and stabilization. CHAPS was used to avoid protein aggregation during concentration of the recombinant stromelysin-3 (ST3) catalytic domain and was required to stabilize the protein, allowing its crystallization. The crystal structure of the complex between the ST3 catalytic domain and a phosphinic inhibitor shows two CHAPS molecules binding to ST3 in two different orientations. One CHAPS molecule is masking a hydrophobic surface of the protein, thus avoiding protein aggregation. This detergent molecule is also involved in packing interactions. The other detergent molecule is located in a pocket formed by the N- and C-terminal parts of the ST3 and stabilizes a loop that normally binds a Ca atom.