@article{maciag_mackenzie_tucker_schipper_swartz_clark_2016, title={Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection}, volume={113}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1603549113}, abstractNote={Significance
          The interconversion of states in the caspase-3 native ensemble is affected by binding of ligands that either stabilize or destabilize active-site loops. It is not clear how the ensemble is regulated in cells, aside from modulating levels of endogenous caspase inhibitors. We describe a library of caspase-3 variants with activities that vary by more than four orders of magnitude and show that removal of conserved water molecules may provide a strategy to design novel allosteric inhibitors that globally destabilize the active conformation within the ensemble. Our results suggest that posttranslational modifications fine-tune caspase activity by disrupting conserved water networks, and our database provides an approach to examine caspase signaling in cells by modifying caspase-3 activity while simultaneously maintaining endogenous enzyme levels.}, number={41}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Maciag, Joseph J. and Mackenzie, Sarah H. and Tucker, Matthew B. and Schipper, Joshua L. and Swartz, Paul and Clark, A. Clay}, year={2016}, month={Oct}, pages={E6080–E6088} }