Physical Sciences and Mathematics Commons^™

Investigation In To The Stabilizing Effects Of The Modified Base Archaeosine In Trna And The Identification Of The Fluorescent Product Of Base Treatment Of Nad(P)+ Cofactors, Ben Turner

Dissertations and Theses

This dissertation covers two projects linked by their involvement in the modification of tRNA bases.

The first project focused on an investigation of a role for the modified base Archaeosine, the ubiquitous modification in tRNA in the archaeal domain. Initial work was performed on a set of in vitro prepared tRNA modified to feature either the canonical guanine base at position 15, preQ₀ (TGT product) or Archaeosine (ArcS product). There was very little difference in the thermal stability of tRNAs containing these modifications in the halophilic H. volcanii tRNA^Ser or E. coli tRNA^Gln. In tRNA^{Gln …}

Quef And Quef-Like: Diverse Chemistries In A Common Fold, Adriana Bon Ramos

Dissertations and Theses

The tunneling fold (T-Fold) superfamily is a small superfamily of enzymes found in organisms encompassing all kingdoms of life. Seven members have been identified thus far. Despite sharing a common three-dimensional structure these enzymes perform very diverse chemistries.

QueF is a bacterial NADPH-dependent oxidoreductase that catalyzes the reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ₀) to a primary amine (preQ₁) in the queuosine biosynthetic pathway. Previous work on this enzyme has revealed the mechanism of reaction but the cofactor binding residues remain unknown. The experiments discussed herein aim to elucidate the role of residues lysine 80, …

Discovery And Characterization Of The Proteins Involved In The Synthesis Of N⁶-Threonylcarbamoyl Adenosine, A Nucleoside Modification Of Trna, Christopher Wayne Deutsch

Dissertations and Theses

N6-threonylcarbamoyl adenosine (t⁶A) is a universally conserved tRNA modification found at position 37 of tRNAs which decode ANN codons. Structural studies have implicated its presence as a requirement for the disruption of a U-turn motif in certain tRNAs, leading to the formation of properly structured anticodon stem loop. This structure is proposed to enhance the base pairing between U₃₆ of tRNA and A₁ of the codon which aids in translational frame maintenance.

Despite significant effort since its discovery in the 1970s the enzymes involved in its biosynthesis remained undiscovered. Bioinformatic analysis identified two proteins as likely …

Biosynthesis Of Marineosin, A Spiroaminal Undecylprodiginine Natural Product, Shaimaa Mohamed Salem

Dissertations and Theses

Marineosins A and B are two spiroaminal-ring containing tripyrrole compounds isolated from the marine actinomycete, Streptomyces CNQ-617, and were found to possess potent and selective cytotoxic activity against leukemia and melanoma. Marineosins belong to the prodiginines class of natural products, examples of which are undecylprodiginine and streptorubin B. Unlike marineosins, prodiginines structures are characterized by the presence of fully conjugated tripyrrole nucleus linked to an alkyl chain (that lacks any oxygen). Cyclic prodiginines arise from an oxidative cyclization of the alkyl chain onto the tripyrrole, a step catalyzed by Rieske-oxygenase like enzymes such as RedG. The biosynthesis of prodiginines is …