Characterization of Conformational Dynamics of Archaeal Protein Tyrosine Phosphatases
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Alansson, Nikolas Bryan
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Abstract
Protein tyrosine phosphatases have long been studied in bacteria and eukaryotes for therapeutic purposes. Key driver for the varying catalytic rates are conformational dynamics of catalytic loops that change with the loop sequence. While PTPs are thought to originate in archaea, only few archaeal PTPs have been studied. Despite the low available data, the proteins have displayed uncharacteristic loop dynamics and sequence motifs. To this date, no computational studies of archaeal PTPs have been performed. This thesis employs molecular dynamics simulations of the proteins TkPTP and SsoPTP as well as an ancestral archaeal PTP called N64 to characterize the loop dynamics of archaeal PTPs. Of key interest are first the findings that the P-loop undergoes correlated conformational changes and second that the changed D-loop sequence is an adaptation to thermophilic environments. These findings cumulate in the conclusion that the archaeal PTPs contain different conformational dynamics than conventional PTPs. With the new characteristics of archaeal PTP conformational dynamics, these insights help understand the development of an important family of signaling proteins.
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2024-05-01
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