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Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 43 for “"CLPP"”.
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Functions of alternative ClpP subunits in Pseudomonas aeruginosa
… two isoforms of the subunits that form the ClpP peptidase chamber. These isoforms, PaClpP1 and PaClpP2, have not been well characterized previously and their specific functions are largely elusive. This work examines the structures and functions of PaClpP1 and PaClpP2 and proposes a model …
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Synthesis and Design of ClpP Activators as Novel Antibiotics
… the dysregulation of the Casein Protease P, ClpP. Methods. Utilize established chemical methods to synthesize ureadepsipeptides, small-molecule ClpP activators, and ureadepsipeptide hybrids. Assess their effectiveness by using minimum inhibitory concentration assays and in vitro biochemical …
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ClpX interactions with ClpP, SspB, protein substrate and nucleotide
… translocates the unfolded substrate into the ClpP peptidase for degradation. The best characterized degradation signal is the ssrA-degradation tag, which contains a binding site for ClpX and an adjacent binding site for the SspB adaptor protein. I show that the close proximity of these binding …
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Regulation of ClpP : role of substrate gating and activation by ClpX
… of the regulator ClpX and the serine protease ClpP. Proteolysis occurs by ClpX-dependent substrate selection, unfolding, and translocation into the degradation lumen of ClpP, where rapid and relatively non-specific peptide hydrolysis generates small peptide products. Prior work had shown that …
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Evaluation of a Microalgal Bioassay Based on Community Level Physiological Profiling (CLPP)
… on community level physiological profiling (CLPP). Five different mixtures of artificially defined microalgal communities were employed and the changes in substrate utilization patterns by the treatment of hexadecyl trimethyl ammonium chloride (CTAC) were quantified using principal component …
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Biophysical and Biochemical Screening Approaches for Antimicrobial Drug Discovery Targeting S. aureus ClpP
… In this direction the Caseinolytic Protease P (ClpP) is an emerging drug discovery target with significant potential for treatment of recalcitrant biofilm forming infections from pathogens such as Methicillin-resistant Staphylococcus aureus (MRSA) This dissertation highlights the ongoing efforts …
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Translocation and proteolysis by the energy-dependent protease ClpAP : coordination of conformational changes and active site chemistry
… substrates into a protease component (e.g., ClpP) where degradation occurs. This thesis addresses the communication between ClpA and ClpP required to efficiently translocate and degrade protein substrates. Synchrotron hydroxyl radical footprinting is used to show that the ClpA D2 loop, …
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Identifying the requirement and mechanism of the dynamic yet kinetically stable ClpXP interface
… Escherichia coli. ClpX is a AAA+ hexamer, and ClpP is a self-compartmentalized peptidase. Previous experiments have shown that ATP is required for assembly of active ClpXP complexes. Moreover, the IGF loops of ClpX are known to be important for stabilizing assembly. In Chapter 2, I use …
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Role of communication between subunits and enzymes in ClpXP-mediated substrate unfolding and degradation
… macromolecular complexes and combines with the ClpP peptidase to form ClpXP, a molecular machine with structural and functional similarity to the eukaryotic 26S proteasome. ClpXP consists of hexameric ClpX rings stacked coaxially against the double-ring ClpP₁₄ peptidase. ClpXP's peptidase active …
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Communication & coordination between components of the ClpAP degradation machine
… that functions with the tetradecameric ClpP peptidase to degrade proteins that are damaged, unneeded, or require degradation for regulation. ClpA has two distinct, stacked rings, termed D1 and D2, constructed from hexamerization of subunits each containing two AAA+ modules. ClpA’s twelve …
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Structural Principles of Substrate Recognition and Unfolding by the ClpAP and ClpXP AAA+ Proteases
… single-ring ClpX unfoldase in complex with the ClpP peptidase. Using covalently crosslinked ClpA–ClpP complexes, I interrogate the symmetry mismatch between the ClpA hexamer and the ClpP heptamer interface to establish that rotation of ClpA relative to ClpP is not required for proteolytic …
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Untersuchungen zum Einfluss der ATP-abhängigen Protease ClpXP auf die Regulation und Expression Virulenz-assoziierter Gene des uropathogenen E. coli Stammes 536
… Sie besteht aus zwei Komponenten, der Protease ClpP und der ATPase ClpX, welche für die Substratspezifität verantwortlich ist und zusätzlich als Chaperon wirken kann. Durch den gezielten Abbau globaler Regulatoren wie dem alternativen Sigmafaktor RpoS kommt die regulatorische Funktion der …
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Molekularbiologische Untersuchungen zur Eignung Virulenz-relevanter Faktoren als Zielstrukturen für die Entwicklung neuer Antibiotika gegen Staphylococcus aureus
… noch nicht charakterisiert waren. Die Zielgene (clpP, purH, ssrA und smpB) in S. aureus sollten deletiert werden, um ihre Überlebensnotwendigkeit in vitro- und in vivo zu überprüfen. Eine Deletion gelang bei den Genen clpP und purH, die somit als nicht essenziell in S. aureus zu betrachten sind. …
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Assessment of potential antibacterial drug targets
… ligase (Ddl), caseinolytic protease subunit P (ClpP), and the dihydrofolate synthase:folyl-poly-glutamate synthase (bifunctional protein FolC). X-ray crystallography was used to determine protein structures of KynB, Ddl and ClpP from various bacteria. Additionally, different enzymatic and …
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Nucleotide binding and conformational switching in the hexameric ring of a AAA+ machine
… unfold and translocate target proteins into the ClpP peptidase for degradation. X-ray crystal structures show that some ClpX subunits occupy nucleotide-loadable conformations and others occupy unloadable conformations. Furthermore, biochemical evidence suggests that multiple classes of …
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Mechanistic studies of the AAA+ molecular motor ClpXP
… translocates them into the associated peptidase, ClpP. ClpX utilizes the energy from ATP hydrolysis to pull on bound substrates, destabilizing folded substrates and denaturing them, before they are translocated through the pore of ClpX into ClpP. As a representative of the AAA+ superfamily, …
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Mechanistic studies of a AAA+ protease
… unfoldase and polypeptide translocase and the ClpP compartmental peptidase. ClpX binds a substrate by an unstructured degradation tag and then, by multiple rounds of ATP-binding and hydrolysis, unfolds and translocates the substrate into the proteolytic chamber of ClpP. To study the features …
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A structured approach to production control in integrated manufacturing systems
… Integrated Production Planning and Control (ClPP&C) system, and second, to formulate and solve specific mathematical models which are nested in the developed framework. The framework functions as a "city plan" for the production control activity in a CIMS environment, while the mathematical …
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Mitochondrial Unfolded Protein Response Regulator Atf5 In Mitochondrial Targeted Therapies In Aml
… and proteases such as HSP60, LonP1 and ClpP, aiding in the restoration of mitochondrial protein pool homeostasis. However, the cell-protective roles of UPR<sup>mt</sup> in the context of mitochondrial stress-induced cell death in AML has not been well explored. We demonstrate that AML …
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