Restricted Research - Award List, Note/Discussion Page

Fiscal Year: 2018

1976  The University of Texas at Arlington  (75794)

Principal Investigator: Brad S. Pierce

Total Amount of Contract, Award, or Gift (Annual before 2011): $ 419,400

Exceeds $250,000 (Is it flagged?): Yes

Start and End Dates: 7/30/17 - 7/30/20

Restricted Research: YES

Academic Discipline: Department of Chemistry and Biochemistry

Department, Center, School, or Institute: College of Science

Title of Contract, Award, or Gift: Monooxygenase/arylamine N-oxygenase activity within a single non-heme diiron enzyme (MiaE)

Name of Granting or Contracting Agency/Entity: National Science Foundation (NSF)

Program Title: N/A
CFDA Linked: Mathematical and Physical Sciences


Non-heme diiron enzymes are a ubiquitous family of enzymes capable of catalyzing an amazing diversity of biological oxidations (mono- and dioxygenation, fatty acid desaturation, iron sequestration, and post-translational modification of tRNA).  Among these enzymes, it has been observed that single amino acid perturbations within the first Fe-coordination sphere have a profound impact on the nature of transient intermediates produced following O2-activation and the extent of substrate oxidation.  For example, within the bacterial multicomponent monooxygenase (BMM) superfamily, the hydroxylase component diiron site is coordinated by 2-histidine and 4-carboxylate (Asp or Glu) residues [2-His/4-carboxylate].  Once the resting (diferric) enzyme is primed by 2 exogenous electrons, the reduced (diferrous) active site is capable of reductively activating molecular oxygen to catalyze the 2-electron oxidation of its specific substrate.  By contrast, a small number of enzymes have been identified which contain an additional His-residue coordinated to one of the two Fe-sites; resulting in a [3-His/4-carboxlate] diiron cluster.  Among these are the arylamine N-oxygenase class of non-heme diiron enzymes AurF and CmlI.  These enzymes catalyze a remarkable 6-electron oxidation of arylamine (R-NH3) substrates to yield a nitroaryl (R-NO2) product. The proposed activities focus on the characterization of an unusual non-heme diiron enzyme (MiaE) isolated from Salmonella typhimurium (St MiaE).  This enzyme catalyzes the O2-dependent hydroxylation of a hypermodified tRNA nucleotide at position 37 (ms2i6A37) to produce 2-methylthio-N6-(4-hydroxyisopentenyl)-adenosine (ms2io6A37).  The [2-His/4-carboxylate] active site of St MiaE is typical of the diiron hydroxylase enzymes within the BMM superfamily.  However, rather than the heterotrimeric dimer configuration (abg)2 typically found among these enzymes, St MiaE exhibits as monomeric (a) protein ….

Discussion: No discussion notes


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