Highlights

Understanding molecular mechanisms in the inflammatory response How are the molecules that trigger asthma produced? Marcia Newcomer, Biological Sciences leukotrienes trigger asthma and have also been linked to atherosclerosis the Fe-containing enzyme lipoxygenase (LOX) initiates the synthesis of leukotrienes human LOX are difficult to handle – use a similar protein from coral

What is the structure of the site that binds the substrate and initiates the synthesis of leukotrienes?

PROTEIN CRYSTALLOGRAPHY (PX): determine molecular structures with x-ray diffraction

a protein crystal is a uniform array of individual proteins

Prepare crystals of the protein of interest-in this case LOX Diffraction pattern contains information on the arrangement of the LOX enzymes in the crystal AND the arrangement of the atoms WITHIN A SINGLE ENZYME PX diffraction pattern is spots of scattered x-rays of different intensities

• analysis of diffraction pattern provides structure of the enzyme initiating inflammatory responses

the enzyme has an unusual U-shaped channel this channel is consistent with chemical activity work underway to develop means to block the channel