التفاصيل البيبلوغرافية
| العنوان: |
Part 1. The role of nickel in carcinogenesis, methanogenesis and transcriptional regulation. Part 2. An X-ray absorption study of Desulfovibrio vulgaris superoxide reductase |
| المؤلفون: |
Carrington, Paul Edward |
| المصدر: |
Doctoral Dissertations Available from Proquest. |
| بيانات النشر: |
ScholarWorks@UMass Amherst. |
| المجموعة: |
University of Massachusetts, Amherst |
| مصطلحات موضوعية: |
Chemistry |
| الوصف: |
Nickel containing proteins play a role in several important biological processes, including methanogenesis (MCR) and superoxide detoxification (NiSOD). However, nickel is also known to mediate carcinogenesis, probably through a process involving coordination to histone proteins within the nucleosome. Therefore, nickel homeostasis must be tightly regulated. In many bacteria and archaea this function is performed by the Nik system. The NikABCDE protein assembly transports nickel into the cell, the transcription of which is repressed by the nickel binding protein, NikR. X-ray absorption spectroscopy (XAS) is a sensitive probe for geometry and ligand type. A combination of model studies and XAS was used to analyze the structural changes that occur at the nickel sites of the enzymes NiSOD, NikR, and MCR. XAS was also used to identify the mode by which nickel may bind to His residues in histone H4. Mutagenesis and XAS studies indicate that the high-affinity nickel site in NikR has square planar geometry and has an N2OS-donor ligand environment composed of His, Glu and Cys ligands. XAS studies further reveal structural changes that occur upon DNA-binding and as a result of mutations in the DNA- and Ni-binding domains. These results suggest that there is communication between the DNA- and Ni-binding domains of the protein. Investigation of the active site of MCR in the EPR active forms MCR red1 and MCRox1 and in the epr silent, Ni(II) forms MCR silent, and MCRox1-silent show that in all four states, nickel is hexacoordinate. The only significant difference being in the nature of the upper axial ligand. Resonance Raman and model studies of the tetrapyrrole cofactor F430, indicate that activation of MCR involves reduction of a C=N bond that likely primes the enzyme for catalysis. In all known anaerobes, superoxide detoxification is performed by iron containing superoxide reductases (SORs). XAS studies on samples of the reduced and photo-reduced, ‘oxidized’ forms of FeSOR from D. vulgaris were performed to determine the extent to which reduction affects ligation. Data collected on the cyanide adduct of the oxidized form indicated that inhibition involves displacement of a Cys-S ligand. |
| Original Identifier: |
oai:scholarworks.umass.edu:dissertations-3778 |
| نوع الوثيقة: |
Text |
| اللغة: |
English |
| الإتاحة: |
https://scholarworks.umass.edu/dissertations/AAI3096267Test |
| رقم الانضمام: |
edsndl.UMASS.oai.scholarworks.umass.edu.dissertations.3778 |
| قاعدة البيانات: |
Networked Digital Library of Theses & Dissertations |
