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You searched for +publisher:"Rutgers University" +contributor:("Nieuwkoop, Andrew"). Showing records 1 – 2 of 2 total matches.

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Rutgers University

1. Hernandez, Nancy, 1991-. Towards overcoming the deficiencies of recently evolved biodegradative enzymes.

Degree: PhD, Chemistry and Chemical Biology, 2019, Rutgers University

This thesis describes a computational protein engineering approach, which utilizes protein assemblies and enzyme engineering, for the biodegradation of an endocrine disruptor and common pollutant, atrazine, and describes all the experimental approaches that were used to further characterize the designed enzymes. A computational generalizable approach for designing fusion proteins that can self-assembly into fractal-like morphologies on the 10 nm – 10 µM length scale was developed. This approach will allow for any set of oligomeric proteins (with cyclic, dihedral, and other symmetries) to form multivalent connections along with designed flexible loops enabling the control of size of a fractal shaped assembly. Our current approach utilizes the SH2 binding domain-pY peptide to allow for a stimulus control of assembly formation through the post-translational modification of phosphorylation. This same generalizable approach can be applied to other metabolic pathways with other domain-peptide recognition proteins with various different responsiveness to other chemicals or physical stimuli. The phase to phase transition that the assembly produces under self-assembly has the potential to provide various applications, such as creating protein-based nanobiomaterials or creating nanocages (in our case protein fractals) to sequester antibodies and easily precipitate out the antibody as needed. In addition to engineering a stimulus responsive protein fractal assembly, the bottle neck enzyme in the biodegradation of atrazine, atzC, was computationally engineered to improve the catalytic efficiency of other known pollutants, N-t-butylammelide and ammelide. This general approach for computationally designing the active site of an enzyme by probing with energetically acceptable substitutions in the various shells of the protein (first and second shell), not including the active site, but instead focusing on mutations nearby the active site resulted in successfully designing variants of atzC with a broadened s-triazine substrate spectrum. To summarize, this dissertation presents a novel and innovative approach for engineering fractal self-assembly of enzymes and explores the design approach for engineering an enzyme with limited abilities for novel substrates.

Advisors/Committee Members: Khare, Sagar D (chair), Berman, Helen (internal member), Nieuwkoop, Andrew (internal member), Nanda, Vikas (outside member), School of Graduate Studies.

Subjects/Keywords: Protein engineering; Atrazine  – Biodegradation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Hernandez, Nancy, 1. (2019). Towards overcoming the deficiencies of recently evolved biodegradative enzymes. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/60164/

Chicago Manual of Style (16th Edition):

Hernandez, Nancy, 1991-. “Towards overcoming the deficiencies of recently evolved biodegradative enzymes.” 2019. Doctoral Dissertation, Rutgers University. Accessed July 07, 2020. https://rucore.libraries.rutgers.edu/rutgers-lib/60164/.

MLA Handbook (7th Edition):

Hernandez, Nancy, 1991-. “Towards overcoming the deficiencies of recently evolved biodegradative enzymes.” 2019. Web. 07 Jul 2020.

Vancouver:

Hernandez, Nancy 1. Towards overcoming the deficiencies of recently evolved biodegradative enzymes. [Internet] [Doctoral dissertation]. Rutgers University; 2019. [cited 2020 Jul 07]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60164/.

Council of Science Editors:

Hernandez, Nancy 1. Towards overcoming the deficiencies of recently evolved biodegradative enzymes. [Doctoral Dissertation]. Rutgers University; 2019. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/60164/


Rutgers University

2. Yang, Xue, 1991-. Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases.

Degree: PhD, Chemistry and Chemical Biology, 2020, Rutgers University

Alpha-synuclein (αSynuclein) accumulation and aggregation is related to many neurodegenerative diseases like Alzheimer's diseases, Parkinson’s diseases, and dementia with Lewy bodies. However, the mechanism of αSynuclein aggregation and the relationship between aggregation pathways and toxicity are still unclear. Beta-synuclein (βSynuclein) is a homologue protein of αSynuclein with high sequence similarity but plays a different role in neurodegenerative diseases. βSynuclein has shown anti-Parkinson capacity in mouse models. In this work, we used βSynuclein as a comparison to answer why αSynuclein fibrils are good templates for seeding aggregation and what kind of interactions promote aggregate formation or inhibition. The work in this thesis explores structure, toxicity, dynamic and seeding aggregation capacity of different αSynuclein oligomers and fibrils which provide critical information for therapeutic targets and designs. By characterizing and comparing αSynuclein, βSynuclein and α/β co-incubated fibrils, we suggest that the stability and dynamics of the fibrils play an important role in controlling the fibril seeding aggregation ability. However, both αSynuclein and βSynuclein fibrils show similar cellular toxicity which suggest that seeding monomer aggregation is not the only contribution for fibril toxicity. Using solution NMR, we show that the initial step for fibril seeding is through interactions at the first 40 residues of the N-terminus. The interactions between αSynuclein stable oligomers and monomers are primarily located at the first 12 residues which results in inhibiting fibril seeding aggregation processes through competing interactions. Coupling these facts together suggests that peptides or small molecular targets that interact with the N-terminus of αSynuclein may be a good approach to inhibit αSynuclein seeding processes and increase the dynamics of fibril packing interfaces can be novel strategies to reduce amyloid toxicity.

Advisors/Committee Members: Baum, Jean (chair), Khare, Sagar (internal member), Nieuwkoop, Andrew (internal member), Mouradian, Maral (outside member), School of Graduate Studies.

Subjects/Keywords: Aggregation; Synucleins

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Yang, Xue, 1. (2020). Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/62585/

Chicago Manual of Style (16th Edition):

Yang, Xue, 1991-. “Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases.” 2020. Doctoral Dissertation, Rutgers University. Accessed July 07, 2020. https://rucore.libraries.rutgers.edu/rutgers-lib/62585/.

MLA Handbook (7th Edition):

Yang, Xue, 1991-. “Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases.” 2020. Web. 07 Jul 2020.

Vancouver:

Yang, Xue 1. Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases. [Internet] [Doctoral dissertation]. Rutgers University; 2020. [cited 2020 Jul 07]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/62585/.

Council of Science Editors:

Yang, Xue 1. Investigation of protein - protein interactions underlying alpha-synuclein aggregation in Parkinson's diseases. [Doctoral Dissertation]. Rutgers University; 2020. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/62585/

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