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University of Massachusetts Amherst

Theses/Dissertations

2019

Caspase

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Full-Text Articles in Life Sciences

Probing Apoptotic Caspase Allostery And Exosite Interactions For Alternative Regulation, Derek J. Macpherson Mar 2019

Probing Apoptotic Caspase Allostery And Exosite Interactions For Alternative Regulation, Derek J. Macpherson

Doctoral Dissertations

Programmed cell death, or apoptosis is a critical homeostatic pathway that monitors the balance of cell life and death. Apoptosis is regulated by a class of enzymes known as the cysteine aspartic proteases, or the caspases. The 12 human caspases that play important roles in the progression and regulation of apoptosis and inflammation. Caspases are tightly regulated by numerous factors including enzymatic activation, post-translational modifications, metal ligand binding, and protein modulation. Aberrant caspase activation and regulation has been implicated in the progression of numerous diseases such as proliferative diseases and neurodegeneration. The deeply entwined nature of caspases and apoptosis makes …


Active Site Design And Exploitation Of Allosteric Sites In Proteases, Maureen Hill Mar 2019

Active Site Design And Exploitation Of Allosteric Sites In Proteases, Maureen Hill

Doctoral Dissertations

Proteases are powerful enzymes with the intrinsic ability to proteolytically cleave other proteins, which often leads to a gain or loss of function. While proteases from the same family often share high similarity in the active site region, distal sites on the enzyme, such as allosteric sites, can differentiate closely related enzymes and allow for specific regulation. This dissertation investigates two different types of proteases, including the viral proteases from both Zika and dengue virus and the mammalian caspase proteases, and contributes significantly to the understanding of both allosteric sites and exosites in these enzymes. Flaviviruses, including Zika virus and …