@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}, 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} }
 @article{mackenzie_schipper_england_thomas_blackburn_swartz_clark_2013, title={Lengthening the Intersubunit Linker of Procaspase 3 Leads to Constitutive Activation}, volume={52}, ISSN={["0006-2960"]}, DOI={10.1021/bi400793s}, abstractNote={The conformational ensemble of procaspase 3, the primary executioner in apoptosis, contains two major forms, inactive and active, with the inactive state favored in the native ensemble. A region of the protein known as the intersubunit linker (IL) is cleaved during maturation, resulting in movement of the IL out of the dimer interface and subsequent active site formation (activation-by-cleavage mechanism). We examined two models for the role of the IL in maintaining the inactive conformer, an IL-extension model versus a hydrophobic cluster model, and we show that increasing the length of the IL by introducing 3-5 alanines results in constitutively active procaspases. Active site labeling and subsequent analyses by mass spectrometry show that the full-length zymogen is enzymatically active. We also show that minor populations of alternately cleaved procaspase result from processing at D169 when the normal cleavage site, D175, is unavailable. Importantly, the alternately cleaved proteins have little to no activity, but increased flexibility of the linker increases the exposure of D169. The data show that releasing the strain of the short IL, in and of itself, is not sufficient to populate the active conformer of the native ensemble. The IL must also allow for interactions that stabilize the active site, possibly from a combination of optimal length, flexibility in the IL, and specific contacts between the IL and interface. The results provide further evidence that substantial energy is required to shift the protein to the active conformer. As a result, the activation-by-cleavage mechanism dominates in the cell.}, number={36}, journal={BIOCHEMISTRY}, author={MacKenzie, Sarah H. and Schipper, Joshua L. and England, Erika J. and Thomas, Melvin E., III and Blackburn, Kevin and Swartz, Paul and Clark, A. Clay}, year={2013}, month={Sep}, pages={6219–6231} }
 @article{walters_schipper_swartz_mattos_clark_2012, title={Allosteric modulation of caspase 3 through mutagenesis}, volume={32}, ISSN={["0144-8463"]}, DOI={10.1042/bsr20120037}, abstractNote={A mutation in the allosteric site of the caspase 3 dimer interface of Val266 to histidine abolishes activity of the enzyme, and models predict that the mutation mimics the action of small molecule allosteric inhibitors by preventing formation of the active site. Mutations were coupled to His266 at two sites in the interface, E124A and Y197C. We present results from X-ray crystallography, enzymatic activity and molecular dynamics simulations for seven proteins, consisting of single, double and triple mutants. The results demonstrate that considering allosteric inhibition of caspase 3 as a shift between discrete ‘off-state’ or ‘on-state’ conformations is insufficient. Although His266 is accommodated in the interface, the structural defects are propagated to the active site through a helix on the protein surface. A more comprehensive view of allosteric regulation of caspase 3 requires the representation of an ensemble of inactive states and shows that subtle structural changes lead to the population of the inactive ensemble.}, number={4}, journal={BIOSCIENCE REPORTS}, author={Walters, Jad and Schipper, Joshua L. and Swartz, Paul and Mattos, Carla and Clark, A. Clay}, year={2012}, month={Aug}, pages={401–411} }
 @article{schipper_mackenzie_sharma_clark_2011, title={A bifunctional allosteric site in the dimer interface of procaspase-3}, volume={159}, ISSN={["1873-4200"]}, DOI={10.1016/j.bpc.2011.05.013}, abstractNote={The dimer interface of caspase-3 contains a bifunctional allosteric site in which the enzyme can be activated or inactivated, depending on the context of the protein. In the mature caspase-3, the binding of allosteric inhibitors to the interface results in an order-to-disorder transition in the active site loops. In procaspase-3, by contrast, the binding of allosteric activators to the interface results in a disorder-to-order transition in the active site. We have utilized the allosteric site to identify a small molecule activator of procaspase and to characterize its binding to the protease. The data suggest that an efficient activator must stabilize the active conformer of the zymogen by expelling the intersubunit linker from the interface, and it must interact with active site residues found in the allosteric site. Small molecule activators that fulfill the two requirements should provide scaffolds for drug candidates as a therapeutic strategy for directly promoting procaspase-3 activation in cancer cells.}, number={1}, journal={BIOPHYSICAL CHEMISTRY}, author={Schipper, Joshua L. and MacKenzie, Sarah H. and Sharma, Anil and Clark, A. Clay}, year={2011}, month={Nov}, pages={100–109} }
 @misc{mackenzie_schipper_clark_2010, title={The potential for caspases in drug discovery}, volume={13}, number={5}, journal={Current Opinion in Drug Discovery & Development}, author={MacKenzie, S. H. and Schipper, J. L. and Clark, A. C.}, year={2010}, pages={568–576} }