The crystal structure of human matrix metalloproteinase type-2 (MMP-2), a key target for several anticancer therapies currently in trials, has now been solved to a 2.8Å resolution (Science 284, 1667–1670, 1999). MMP-2 is secreted as a proenzyme that becomes partially activated upon proteolysis by activators. By breaking down connective tissue, it is thought to allow tumors to grow new blood vessels and encroach upon surrounding tissues. Researchers had previously mapped the structure of limited portions of the protein, but Karl Tryggvason and colleagues from the Karolinska Institute (Stockholm, Sweden) used a combination of x-ray crystallography and molecular replacement modeling to resolve the complete structure of the full-length proform of the enzyme. Although the active site is similar to many other MMPs, Trygvasson's structure reveals several other targets for designing more specific MMP-2 inhibitors: "One could design drugs that inhibit binding of TIMP-2 [tissue inhibitor of MMP-2] to the hemopexin domain, thereby preventing activation," he suggests. Using computer modeling, the Swedish team is currently collaborating with BioStratum (Research Triangle Park, NC) to further refine inhibitors.