X-Ray Crystal Structures of MAC-1 and LFA-1 I Domains. Eric T. Baldwin, Nancy C. Horton, Carol A. Baker, Garold L. Bryant, Jr., Kimberly A. Curry, Michael B. Fairbanks, Barry C. Finzel, Robert L. Garlick, Robert L. Heinrikson, Laura C. Kelly, Anna N. Mildner, Veronica T. Mutchler, Che-Shen C. Tomich, and Keith D. Watenpaugh. Pharmacia and Upjohn, Inc., Discovery Research, Kalamazoo, MI 49007

The Beta-2 integrins are the subject of intense interest since these adhesion molecules play a role in leukocyte mediated inflammatory events. The observation that a deficiency in these receptors results in an inability to recruit neutrophils to the site of infection suggested that drugs specific for these receptors might block chronic or acute inflammation. A variety of antibody binding, site-directed mutagenesis and metal binding studies have suggested that a metal binding site within a 180 amino acid fragment of the alpha subunit of these integrins (I domain) is critical for leukocyte binding to ICAM on endothelial cells. The I domain from Mac-1 and Lfa-1 has been the subject of a number of previous crystallographic investigations. We present the X-ray crystal structure of Mac-1 I domain in a new crystal context: metal free, with Mg⁺⁺ ion, Mn⁺⁺ ion and Cd⁺⁺ ion. The crystal structure of Lfa-1 I domain with Mn⁺⁺ ion is also presented. These new crystal structures will be compared with the other published X-ray structures.