Schematic representation of the active site of TEM-1 β-lactamase. Residues targeted for saturation mutagenesis (Glu-104, Tyr-105, Gly-238, Glu-240, and Arg-244) are represented in blue according to their Connolly surface, defined by a 1.6 Å solvent radius. These amino acids belong to two distinct faces of the active-site cavity. Residues known to be involved in the catalytic mechanism (Ser-70, Lys-73, Ser-130, and Glu-166) are colored in red. The cocrystallized BZ is shown in ball-and-sticks representation and is displayed to illustrate its proximity to the targeted active-site positions. PDB coordinates 1FQG. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]