Application Note: Crystal Structure Determination of a Key Processing Enzyme in Huntington’s Disease
30 October 2012
Although the molecular basis of Huntington’s Disease (HD) is not fully understood it has been postulated that inhibition of caspase-6 activity may prove to be neuroprotective in HD. Crystal structures of the enzyme in its active conformation would be a huge advantage for the design of caspase-6-specific inhibitors. This application note from TTP Labtech describes the use of the mosquito® Crystal to screen for and optimize crystallization conditions to obtain the structure of caspase-6 in its active state and a caspase-6 inhibitor complex, consisting of caspase-6 and the non-specific and irreversible caspase inhibitor, Z-VAD-FMK. The reproducibility and accuracy of mosquito Crystal during primary screen set-up and optimization studies were crucial to obtaining well-diffracting crystals from a limited amount of sample in a time-efficient way.