Serine hydrolases represent one of the largest and most diverse classes of enzymes in higher eukaryotes, collectively composing about 3% of the predicted Drosophila proteome (Rubin et al., 2000) and about 1% of all predicted expressed human genes (Lander et al., 2001) . Serine hydrolases are involved in a variety of physiological and pathological processes including blood coagulation (Kalafatis et al., 1997) , T cell cytotoxicity (Smyth et al., 1996) , inflammation (Bonventre et al., 1997) , neural plasticity (Yoshida and Shiosaka, 1999) , neurotransmitter catabolism (Taylor, 1991; Cravatt et al., 1996) , peptide/protein processing (Steiner, 1998) , protein/lipid digestion (Lowe, 1997) , angiogenesis (Mignatti and Rifkin, 1996) , emphysema (Kato, 1999) , and cancer (DeClerck et al., 1997) . Serine hydrolases also perform crucial functions in bacteria and viruses, where they contribute to pathogen life cycle (Steuber and Hilgenfeld, 2010) , virulence (White et al., 2011) , and drug resistance (Damblon et al., 1996) . Most enzymes hydrolyze metabolites, peptides or post-translational ester and thioester modifications on proteins. Because of the biological importance of serine hydrolases, clinically approved drugs target members of this enzyme class to treat diseases such as obesity (Henness and Perry, 2006) , diabetes (Thornberry and Weber, 2007) , microbial infections (Kluge and Petter, 2010) , and Alzheimer's disease (Racchi et al., 2004) .