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You searched for subject:(heme binding protein). Showing records 1 – 2 of 2 total matches.

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University of Western Ontario

1. Laakso, Holly A. Iron and Copper Homeostasis in Staphylococcus aureus.

Degree: 2018, University of Western Ontario

All microorganisms require transition metals for key metabolic processes, thus during infection microbial access to essential metals is tightly regulated by the host in a process termed nutritional immunity. Iron acquisition is critical to the pathogenesis of the formidable human pathogen, Staphylococcus aureus, which utilizes heme-uptake systems and two high-affinity iron-scavenging siderophores, staphyloferrin A (SA) and staphyloferrin B (SB) for iron acquisition. In this study, I identify sbnI as encoding a transcription factor required for expression of genes in the sbn operon, the biosynthetic operon for SB synthesis. I also show that SbnI is a novel hemoprotein, where binding to heme abrogates its ability to bind DNA. Thus this work proposes a novel mechanism in which S. aureus controls SB synthesis in response to heme. Although free iron is scarce in the host, copper at the host-pathogen interface is found in excess. Copper is highly reactive and in macrophages is imported into phagosomes where it exerts bactericidal effects. S. aureus flourishes within macrophages and therefore must resist copper-mediated killing. I demonstrate that the USA300 strain of Community-Associated MRSA relies on CopAZ and CopBL for copper detoxification; where CopA and newly identified CopB are copper-translocating efflux pumps, CopZ is a copper-binding chaperone, and CopL is a novel copper-responsive lipoprotein. Finally, CopAZ, in accord with CopBL, aid in S. aureus survival in murine macrophages. This study examines two important facets of nutritional immunity and the virulence factors used by S. aureus to overcome obstacles posed by the host in maintaining metal homeostasis.

Subjects/Keywords: Staphylococcus aureus; iron acquisition; siderophores; transcription factor; heme-binding protein; copper toxicity; CopA; CopB; lipoprotein; macrophage; Pathogenic Microbiology

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

APA (6th Edition):

Laakso, H. A. (2018). Iron and Copper Homeostasis in Staphylococcus aureus. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/5204

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Laakso, Holly A. “Iron and Copper Homeostasis in Staphylococcus aureus.” 2018. Thesis, University of Western Ontario. Accessed December 16, 2018. https://ir.lib.uwo.ca/etd/5204.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Laakso, Holly A. “Iron and Copper Homeostasis in Staphylococcus aureus.” 2018. Web. 16 Dec 2018.

Vancouver:

Laakso HA. Iron and Copper Homeostasis in Staphylococcus aureus. [Internet] [Thesis]. University of Western Ontario; 2018. [cited 2018 Dec 16]. Available from: https://ir.lib.uwo.ca/etd/5204.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Laakso HA. Iron and Copper Homeostasis in Staphylococcus aureus. [Thesis]. University of Western Ontario; 2018. Available from: https://ir.lib.uwo.ca/etd/5204

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Texas – Austin

2. -5387-6362. The mechanism study of fumitremorgin B dioxygenase and engineered human cystathionine gamma lyase.

Degree: Biochemistry, 2018, University of Texas – Austin

Peroxy-containing compounds represent a large class of natural products with many demonstrated beneficial effects to human health. Yet, very little is known about how endoperoxide functionality is incorporated into the natural products. In the first section of this dissertation, we have done the biochemical and structural research on the protein Fumitremorgin B dioxygenase, which is the first non-heme iron enzyme catalyzing an endoperoxide formation reaction. This work discloses mechanistic understanding to explain this unprecedented transformation. Distinct from all currently known α-ketoglurarate-dependent mononuclear non-heme iron enzymes, FtmOx1 incorporates molecular oxygen into the product without O-O bond scission, suggesting a novel mechanism. Indeed, the structural data reveal a surprising and unique arrangement of α-ketoglutarate (α-KG). Once the co-factor α-KG binds to the iron center, the remaining site for oxygen binding and activation is completely shielded from substrate access. This is in dramatic contrast to currently characterized α-ketoglurarate-dependent mononuclear non-heme iron enzymes, in which the oxygen binding site directly faces the substrate to be oxidized. From the crystal structure, we identify a tyrosine residue (Y224) as the residue shielding the mononuclear iron center from substrate access. The following biochemical study has shown that upon Y224A and Y224F mutation, the reaction is shifted from endoperoxide formation to a traditional α-ketoglurarate-dependent mononuclear non-heme iron enzyme catalyzed oxidative hydroxylation reaction. Further EPR study and pre-steady state analysis suggested an organic radical formed during catalysis. Those structural and biochemical data allow us to formulate a mechanistic model to account for this unprecedented endoperoxide formation reaction in which Y224 will form a tyrosyl radical and acting as a bridge to connect between the iron center and the substrate. Cancer cells exhibit different metabolism compared to normal tissue, this has been shown to be a successful target in clinical. It has been found that some types of cancer are dependent on particular amino acids since they are not able to synthesize these amino acids themselves. Thus the strategy of starving tumor cell from its specific essential amino acid has great potential in anti-tumor therapeutic development. To consume the essential amino acid L-Methionine, human cystathionine-γ-lyase has been engineered to utilize methionine as substrate. One of the variants (hCGL-NLV) derived from this strategy showed altered specificity from cystathionine to methionine with improved half life compared with bacterial methionine gamma lyase. To understand the structural rationale to direct further bioengineering design, we obtained the crystal structures of this variant CGL-NLV in both an active and inactive conformations. The comparison between the two forms of hCGL-NLV highlighted a salt bridge between active site essential arginine residue (R62) and co-factor PLP that is attenuated upon high salt… Advisors/Committee Members: Zhang, Yan Jessie (advisor), Georgiou, George (committee member), Hackert, Marvin L. (committee member), Iverson, Brent L. (committee member), Whitman, Chris P. (committee member).

Subjects/Keywords: Endoperoxide formation; Tyrosyl radical; Non-heme iron protein; Novel α-ketoglutarate binding orientation; CGS-like protein; Engineered enzyme; Salt dependence; Substrate selectivity shift

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

APA (6th Edition):

-5387-6362. (2018). The mechanism study of fumitremorgin B dioxygenase and engineered human cystathionine gamma lyase. (Thesis). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/68396

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

-5387-6362. “The mechanism study of fumitremorgin B dioxygenase and engineered human cystathionine gamma lyase.” 2018. Thesis, University of Texas – Austin. Accessed December 16, 2018. http://hdl.handle.net/2152/68396.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

-5387-6362. “The mechanism study of fumitremorgin B dioxygenase and engineered human cystathionine gamma lyase.” 2018. Web. 16 Dec 2018.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

-5387-6362. The mechanism study of fumitremorgin B dioxygenase and engineered human cystathionine gamma lyase. [Internet] [Thesis]. University of Texas – Austin; 2018. [cited 2018 Dec 16]. Available from: http://hdl.handle.net/2152/68396.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

-5387-6362. The mechanism study of fumitremorgin B dioxygenase and engineered human cystathionine gamma lyase. [Thesis]. University of Texas – Austin; 2018. Available from: http://hdl.handle.net/2152/68396

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

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