Global ETD Search
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 84 for “"substrate recognition"”.
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Substrate recognition by the 26S proteasome
… that specific signals (called degrons) on the substrates are recognised by the proteasome, including ubiquitin and a disordered region. The main focus of this thesis is to better understand how the ubiquitin containing degron binds to intrinsic ubiquitin receptors in the 26S proteasome and how …
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Developing O-GlcNAc transferase inhibitors - insights from substrate recognition
… (OGT), which adds the sugar onto protein substrates and the O-GlcNAc hydrolase (OGA), which removes it. Mass spectrometric analyses have shown that O-GlcNAc can be found on proteins involved in nearly all biological processes, including trafficking, transcription & translation, protein …
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Elucidation and control of substrate recognition during RiPP biosynthesis
… Chapter 2, I report my investigations into the substrate recognition of canonical cyclodehydratases. Recent work suggested that unrelated RiPP modifying enzymes contain structurally similar precursor peptide binding domains. Using profile hidden Markov model comparisons, I discovered related and …
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Mechanisms of substrate recognition by the AAA+ protease HslUV
… My first goal was to understand the rules of substrate recognition. To do so, I performed a variety of experiments on two model proteins: Arc repressor and [chi]cIN repressor. I found that both substrates had common requirements for HslUV degradation, suggesting a conserved mode of recognition …
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INSIGHTS INTO SUBSTRATE RECOGNITION BY THE ANAPHASE PROMOTING COMPLEX (APC)
… (APC). APC adds polyubiquitin chains to numerous substrates, which leads to their subsequent degradation in late mitosis and G1 phase. The selective and timely recognition and degradation of APC substrates is essential for proper cell cycle progression and maintenance of genome stability. However, …
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Direct real-time correlation of protein conformation and substrate recognition
… a protein and its interaction with the cognate substrate exemplify two important biomolecular processes that may be correlated, uncorrelated, or partially correlated. While the degree to which these processes are correlated may bear heavily on the mechanism and regulation of the said protein, an …
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Molecular specificity of substrate recognition and activation in cytochrome P-450(CAM)
… in binding and activation of hydrocarbon substrates by cytochrome P-450$\sb{\rm cam}$. The dependence of the reaction efficiency and specificity on the structural complementarity in the P-450$\sb{\rm cam}$-substrate complex suggests that the active site structure is of paramount importance …
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Assembly and substrate recognition properties of human CCT subunits of the TRiC chaperonin
… aggregation and refolding two different substrates: luciferase (a model substrate) and human [gamma]D-crystallin (H[gamma]D-Crys; a physiological substrate found in the eye lens). To further understand human TRiC, we expressed all of the human CCT subunits, one at a time in E. coli. This …
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Investigation of the Substrate Recognition Characteristics and Kinetics of Mammalian Mitochondrial DNA Topoisomerase I
… of mitochondrial topoisomerase I to its substrate DNA. To study the substrate preference and kinetic parameters of mitochondrial topoisomerase I, selected regions of mammalian mitochondrial DNA (mtDNA) were inserted into pGEM plasmid vectors following a series of modification and …
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Structural Principles of Substrate Recognition and Unfolding by the ClpAP and ClpXP AAA+ Proteases
… perform targeted protein degradation of specific substrates. All AAA+ proteases consist of a hexameric AAA+ unfoldase and a compartmentalized peptidase. AAA+ proteases harness the energy of ATP hydrolysis to mechanically unfold and translocate substrates through the axial channel into the …
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Structural and Functional Analysis of Substrate Recognition and Inhibition of the Multidrug Transporters MRP1 and MRP2
… manner, the mechanism of GSH-dependent MRP1 substrate transport has previously not been understood. Additionally, over the past three decades, multiple small-molecule inhibitors of MRP1 transport have also been identified, with the activity of several inhibitors also determined to be …
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REDEFINING THE SCOPE OF PRENYLATION: DISCOVERY OF “FORBIDDEN” SUBSTRATE RECOGNITION AND DEVELOPMENT OF METHODS UTILIZING PRENYLATED PROTEINS
… to a cysteine residue near the C-terminus of a substrate protein by one of three enzymes: protein farnesyltransferase (FTase), protein geranylgeranyltransferase type I (GGTase-I) or protein geranylgeranyltransferase type II (GGTase-II, also known as Rab GGTase). These covalent modifications can …
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The N-end rule degradation pathway : substrate recognition and staged delivery to the CIpAP protease by the CIpS adaptor protein
… for the degradation of a broad array of substrates and for that reason, a high degree of substrate specificity is required in order to target only desired proteins for destruction. Adaptor proteins can provide ATP-dependent proteases an extra-layer of specificity by binding and delivering …
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Understanding the determinants for substrate recognition, regulation of enzymatic activity and the development of broad-spectrum inhibitors of coronavirus 3-chymotrypsin-like proteases
Coronaviruses include lethal human pathogens like severe acute respiratory syndrome coronavirus (SARS-CoV) and the recently emerged Middle-east respiratory coronavirus (MERS-CoV). Coronavirus also impact global economy by infecting farm animals like pigs (porcine epidemic diarrhea virus, PEDV), …
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Functional and structural studies of AAA+ proteases
… ATPase recognizes, unfolds, and translocates substrates into an associated self-compartmentalized peptidase for degradation. In addition to participating in proteolysis, AAA+ ATPases, by themselves, can unfold and/or remodel macromolecular complexes. However, rigorous characterization of these …
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UNDERSTANDING GENERALIZED ALLOSTERY IN THROMBIN
… further the understanding of thrombin's substrate recognition process and allosteric pathways. Finally, the work concludes with future directions of investigating the allosteric network of thrombin.
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Substrate specificity and functional characterization of sodium/dicarboxylate cotransporters
… helices (TMs) are involved in NaDC1 substrate recognition, with the region of TM 3-4 and the C-terminus required for glutarate while the TM 8-10 region is necessary for adipate transport. Further analysis of these two regions provided evidence that they contained residues important …
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On the Repair of DNA Breaks and the Specificity of the EcoRI Restriction Enzyme
… and double-strand break repair in E. coli, and substrate recognition by the EcoRI endonuclease. Many species of bacteria make restriction-modification systems to destroy foreign DNA that enters the cell. These systems usually consist of an endonuclease that cleaves a specific DNA sequence and a …
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Protein-Protein Interactions and Small Molecule Targeting of the Multisubunit SOCS2-EloBC-Cul5-Rbx2 E3 Ubiquitin Ligase
… by catalysing ubiquitin transfer to specific substrates for proteasomal degradation. SOCS2 is a component of the multisubunit CRL E3 complex (CRL5<sup>SOCS2</sup>). SOCS2 plays important roles in several cancers and is involved in diabetes and inflammatory diseases. This work aims to …
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The Evaluation of Conserved Amino Acids that Influence Polysubstrate Specificity in the Multidrug Resistance Transporter, EmrE
The study of the molecular mechanism of substrate recognition/binding by multidrug resistance transporters has taken different approaches. I have utilized a PCR-driven site-directed mutagenesis analysis to alter conserved amino acid residues within the Escherichia coli small multidrug transporter, …
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