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Full-Text Articles in Biochemistry

Mechanistic And Substrate Specificity Studies On Burkholderia Mallei Quorum Sensing Signal Synthesis Enzyme, Aubrey N. Montebello Aug 2014

Mechanistic And Substrate Specificity Studies On Burkholderia Mallei Quorum Sensing Signal Synthesis Enzyme, Aubrey N. Montebello

Boise State University Theses and Dissertations

Gram-negative bacteria use acyl-homoserine lactone (AHL) based quorum sensing (QS) to regulate the expression of genes that give the bacteria a selective advantage over host defenses and antibiotic treatment. Burkholderia mallei is an antibiotic resistant pathogen that causes Glanders disease. B. mallei BmaI1 AHL-synthase uses octanoyl-Acyl Carrier Protein (C8ACP) and S-adenosyl-L-methionine (SAM) to synthesize the AHL, octanoyl-homoserine lactone (C8HSL). Inhibiting AHL-synthases has been difficult because mechanistic and substrate specificity details for these enzymes are not well understood. Our goal was to determine how BmaI1 activity and enzymatic mechanism changes with nonspecific, variable acyl chain acyl-ACP substrates. We found that catalytic …


Exploration Into The Cellular Effects Of Aziridinomitosenes, Christopher M. Mallory Aug 2014

Exploration Into The Cellular Effects Of Aziridinomitosenes, Christopher M. Mallory

Boise State University Theses and Dissertations

Aziridinomitosenes (AZMs) are organic compounds structurally related to the mitomycins, a class of anti-tumor agents and antibiotics. The cytotoxicity of the mitomycins is correlated to their ability to covalently link complimentary strands of DNA, forming DNA interstrand cross-links (ICLs). Currently, there has been limited investigation into the biological activity of AZMs, likely due to difficulties in their synthesis. Our lab has synthesized and evaluated the cellular effects of two AZMs, (1S, 2S)-6-desmethyl(methylaziridino)mitosene (H/H-AZM) and (1S, 2S)-6-methyl(methylaziridino)mitosene (Me/H-AZM). We hypothesize that AZMs exhibit their cytotoxicity and cellular effects following a similar pathway to that of mitomycin C (MC) including …