Biology Department Seminar

The flexibility of regions involved in catalysis or substrate binding is crucial for enzymatic functions but often leads to disorder in the crystal structures. Through determination of multiple structures in complex with appropriate choices of ligands, it is possible to capture the snapshots of enzymes in motion. This is demonstrated by structural characterization of the naphthoate synthase in the menaquinone biosynthesis pathway, in which the catalytically competent state is trapped by a substrate analogue, revealing a detailed mechanism of an intramolecular Claisen condensation reaction. In the example given by the enoylreductase involved in type II fatty acid biosynthesis, a series of diphenyl ethers with varying residence times with the enzyme are used to trap the flexible substrate-binding loop in the early stages of binding in addition to the equilibrated state, enabling the characterization of the binding pathway and correlation to the inhibition kinetics with the implications to the in vivo activity of antibacterial drugs.