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ABSTRACT A major challenge for science educators is teaching foundational concepts while introducing their students to current research. Here we describe an active learning module developed to teach protein structure fundamentals while supporting ongoing research in enzyme discovery. It can be readily implemented in both entry-level and upper-division college biochemistry or biophysics courses. Preactivity lectures introduced fundamentals of protein secondary structure and provided context for the research projects, and a homework assignment familiarized students with 3-dimensional visualization of biomolecules with UCSF Chimera, a free protein structure viewer. The activity is an online survey in which students compare structure elements in papain, a well-characterized cysteine protease from Carica papaya, to novel homologous proteases identified from the genomes of an extremophilic microbe (Halanaerobium praevalens) and 2 carnivorous plants (Drosera capensis and Cephalotus follicularis). Students were then able to identify, with varying levels of accuracy, a number of structural features in cysteine proteases that could expedite the identification of novel or biochemically interesting cysteine proteases for experimental validation in a university laboratory. Student responses to a postactivity survey were largely positive and constructive, describing points in the activity that could be improved and indicating that the activity was an engaging way to learn about protein structure.