National Center for
4DD8: Adam-8 Metalloproteinase Domain With Bound Batimastat
Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. (2012) 68 p.616-621
The role of ADAM-8 in cancer and inflammatory diseases such as allergy, arthritis and asthma makes it an attractive target for drug development. Therefore, the catalytic domain of human ADAM-8 was expressed, purified and crystallized in complex with a hydroxamic acid inhibitor, batimastat. The crystal structure of the enzyme-inhibitor complex was refined to 2.1 A resolution. ADAM-8 has an overall fold similar to those of other ADAM members, including a central five-stranded beta-sheet and a catalytic Zn(2+) ion. However, unique differences within the S1' binding loop of ADAM-8 are observed which might be exploited to confer specificity and selectivity to ADAM-8 competitive inhibitors for the treatment of diseases involving this enzyme.