A textbook rule about enzyme catalysis is being called into question by Jonathan M. Goodman of the University of Cambridge and Luis Simón of Spain’s University of Salamanca. The duo finds that the long-held adage that an enzyme’s active site stabilizes a reactant’s transition state in order to speed up reactions might not be universally true (J. Org. Chem., DOI: 10.1021/jo901503d). After reviewing hundreds of so-called oxyanion-hole enzyme structures, which catalyze addition reactions to carbonyl groups, Goodman’s team noticed that active-site residues in these enzymes don’t form optimally oriented hydrogen bonds to transition-state atoms. Instead, the hydrogen bonds are twisted around the carbonyl axis by up to 90°, Goodman says. There’s some evolutionary logic behind the twisted bonds. Goodman points out that hydrogen bonding that is too snug might decrease the speed of a reaction because molecules could find interacting with the enzyme too enjoyable to move along quickly. That observation might be useful to scientists designing artificial enzymes and organocatalysts, the researchers suggest.