Theses and Dissertations
Issuing Body
Mississippi State University
Advisor
Fitzkee, Nicholas C.
Committee Member
Lewis, Edwin A.
Committee Member
Foster, Stephen C.
Committee Member
Emerson, Joseph P.
Date of Degree
12-14-2013
Document Type
Graduate Thesis - Open Access
Major
Chemistry
Degree Name
Master of Science
College
College of Arts and Sciences
Department
Department of Chemistry
Abstract
Pin1 is a Prolyl Isomerase that catalyzes cis-trans isomerization of peptides with pSer/Thr-Pro motifs in many cell signaling proteins. This conformational switch is implicated in diseases. Pin1 activity is considered a target for therapeutic applications. Pin1 targets motifs by its N-terminal WW-binding domain. A C-terminal PPIase domain is responsible for catalysis. To understand how Pin1 coordinates its enzymatic activities, it is necessary to probe how the domains behave in the presence of substrates. Here, we used novel (Histone H1 and Sic1) and other existing peptides to characterize the dynamics of Pin1 and impact of substrate binding on inter-domain interactions. Pin1- peptide complexes have been used to show that peptide addition causes a conformational change in the two domains. 15N-relaxation data suggest that the flexibility of these domains depends on the substrate peptide We have constructed a hypothesis about which substrate residues may be important for conferring tight binding and inter-domain interactions.
URI
https://hdl.handle.net/11668/18985
Recommended Citation
Gyamfi, Hawa, "Understanding Binding-Induced Conformational Change in the Pin1 Prolyl Isomerase" (2013). Theses and Dissertations. 4817.
https://scholarsjunction.msstate.edu/td/4817