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Title: Streptococcus pyogenes quinolinate-salvage pathway-structural and functional studies of quinolinate phosphoribosyl transferase and NH 3-dependent NAD + synthetase

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [1]
  1. Department of Chemistry and Biochemistry, University of South Carolina, Columbia SC USA
  2. Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville VA USA
  3. Department of Chemistry and Biochemistry, University of South Carolina, Columbia SC USA, Department of Chemistry, Davidson College, NC USA
Publication Date:
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1374080
Grant/Contract Number:
AC02-06CH11357
Resource Type:
Journal Article: Publisher's Accepted Manuscript
Journal Name:
Federation of European Biochemical Societies (FEBS) Journal
Additional Journal Information:
Journal Name: Federation of European Biochemical Societies (FEBS) Journal; Journal Volume: 284; Journal Issue: 15; Related Information: CHORUS Timestamp: 2018-02-22 23:06:41; Journal ID: ISSN 1742-464X
Publisher:
Federation of European Biochemical Societies
Country of Publication:
United Kingdom
Language:
English

Citation Formats

Booth, William T., Morris, Trevor L., Mysona, David P., Shah, Milan J., Taylor, Linda K., Karlin, Taylor W., Clary, Kathryn, Majorek, Karolina A., Offermann, Lesa R., and Chruszcz, Maksymilian. Streptococcus pyogenes quinolinate-salvage pathway-structural and functional studies of quinolinate phosphoribosyl transferase and NH3-dependent NAD+ synthetase. United Kingdom: N. p., 2017. Web. doi:10.1111/febs.14136.
Booth, William T., Morris, Trevor L., Mysona, David P., Shah, Milan J., Taylor, Linda K., Karlin, Taylor W., Clary, Kathryn, Majorek, Karolina A., Offermann, Lesa R., & Chruszcz, Maksymilian. Streptococcus pyogenes quinolinate-salvage pathway-structural and functional studies of quinolinate phosphoribosyl transferase and NH3-dependent NAD+ synthetase. United Kingdom. doi:10.1111/febs.14136.
Booth, William T., Morris, Trevor L., Mysona, David P., Shah, Milan J., Taylor, Linda K., Karlin, Taylor W., Clary, Kathryn, Majorek, Karolina A., Offermann, Lesa R., and Chruszcz, Maksymilian. Fri . "Streptococcus pyogenes quinolinate-salvage pathway-structural and functional studies of quinolinate phosphoribosyl transferase and NH3-dependent NAD+ synthetase". United Kingdom. doi:10.1111/febs.14136.
@article{osti_1374080,
title = {Streptococcus pyogenes quinolinate-salvage pathway-structural and functional studies of quinolinate phosphoribosyl transferase and NH3-dependent NAD+ synthetase},
author = {Booth, William T. and Morris, Trevor L. and Mysona, David P. and Shah, Milan J. and Taylor, Linda K. and Karlin, Taylor W. and Clary, Kathryn and Majorek, Karolina A. and Offermann, Lesa R. and Chruszcz, Maksymilian},
abstractNote = {},
doi = {10.1111/febs.14136},
journal = {Federation of European Biochemical Societies (FEBS) Journal},
number = 15,
volume = 284,
place = {United Kingdom},
year = {Fri Jul 07 00:00:00 EDT 2017},
month = {Fri Jul 07 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
This content will become publicly available on July 7, 2018
Publisher's Accepted Manuscript

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  • Quinolinic acid phosphoribosyl transferase (QAPRTase, EC 2.4.2.19) is a 32 kDa enzyme encoded by the BNA6 gene in yeast and catalyzes the formation of nicotinate mononucleotide from quinolinate and 5-phosphoribosyl-1-pyrophosphate (PRPP). QAPRTase plays a key role in the tryptophan degradation pathway via kynurenine, leading to the de novo biosynthesis of NAD{sup +} and clearing the neurotoxin quinolinate. To improve our understanding of the specificity of the eukaryotic enzyme and the course of events associated with catalysis, we have determined the crystal structures of the apo and singly bound forms with the substrates quinolinate and PRPP. This reveals that the enzymemore » folds in a manner similar to that of various prokaryotic forms which are {approx}30% identical in sequence. In addition, the structure of the Michaelis complex is approximated by PRPP and the quinolinate analogue phthalate bound to the active site. These results allow insight into the kinetic mechanism of QAPRTase and provide an understanding of structural diversity in the active site of the Saccharomyces cerevisiae enzyme when compared to prokaryotic homologues.« less
  • Group A Streptococcus (GAS) is an exclusive human pathogen that causes significant disease burden. Global regulator RopB of GAS controls the expression of several major virulence factors including secreted protease SpeB during high cell density. However, the molecular mechanism for RopB-dependent speB expression remains unclear. To understand the mechanism of transcription activation by RopB, we determined the crystal structure of the C-terminal domain of RopB. RopB-CTD has the TPR motif, a signature motif involved in protein-peptide interactions and shares significant structural homology with the quorum sensing RRNPP family regulators. Characterization of the high cell density-specific cell-free growth medium demonstrated themore » presence of a low molecular weight proteinaceous secreted factor that upregulates RopB-dependent speB expression. Together, these results suggest that RopB and its cognate peptide signals constitute an intercellular signalling machinery that controls the virulence gene expression in concert with population density. Structure-guided mutational analyses of RopB dimer interface demonstrated that single alanine substitutions at this critical interface significantly altered RopB-dependent speB expression and attenuated GAS virulence. Finally, results presented here suggested that a properly aligned RopB dimer interface is important for GAS pathogenesis and highlighted the dimerization interactions as a plausible therapeutic target for the development of novel antimicrobials.« less
  • Hydrothermal reactions of molybdenum-oxide precursors with polyalcohols in the presence of base yielded two series of mixed-valence oxomolybdenum clusters, the hexadecanuclear species [XH{sub 12}(Mo{sup VI}O{sub 3}){sub 4}Mo{sup V}{sub 12}O{sub 40}]{sup m{minus}}(X=Na{sup +}, m=7; X=2H{sup +}, m=6) and the superclusters [XH{sub n}Mo{sup VI}{sub 6}Mo{sup V}{sub 36}O{sub 109}(OCH{sub 2}){sub 3}CR{sub 7}]{sup m{minus}} (X=Na-(H{sub 2}O){sub 3}{sup +}, m=9, n=13; X=Na(H{sub 2}O){sub 3}{sup +}, m=7, n=15; X=MoO{sub 3}, m=9, n=14; X=MoO{sub 3}, m=10, n=13). In a representative synthesis for the hexadencanuclear class of materials, the hydrothermal reaction of a mixture of Na{sub 2}MoO{sub 4}{center_dot}2H{sub 2}O, MoO{sub 3}, Mo metal, and NH{sub 4}Cl produced (NH{submore » 4}){sub 7}[NaMo{sub 16}(OH){sub 12}O{sub 40}]{center_dot}4h{sub 2}O (1{center_dot}4H{sub 2}O) as red-orange crystals. The compound (Me{sub 3}NH){sub 4}K{sub 2}[H{sub 2}Mo{sub 16}(OH){sub 40}]{center_dot}8H{sub 2}O(2{center_dot}8H{sub 2}O(2{center_dot}8H{sub 2}O) was prepared in a similar fashion. The structure of the anion of 1 consists of an {epsilon}-Keggin core H{sub 12}Mo{sub 12}O{sub 40}, capped on four hexagonal faces by MoO{sub 3} units and encapsulating a Na{sup +} cation. The structure of the oxomolybdenum framework of 2 is essentially identical to that of 1; however, the central cavity is now occupied by 2H{sup +}.« less
  • Trace amounts of H/sub 2/O and limited exposure to air of reaction mixtures of UCl/sub 4/ and 12-crown-4, 15-crown-5, benzo-15-crown-5, 18-crown-6, or dibenzo-18-crown-6 in 1:3 mixtures of CH/sub 3/OH and CH/sub 3/CN resulted in the hydrolysis and oxidation of UCl/sub 4/ to (UO/sub 2/Cl/sub 4/)/sup 2/minus//. In the presence of these crown ethers, it has been possible to isolate intermediate products via crystallization of crown complexes of the (UO/sub 2/Cl/sub 4/)/sup 2/minus// ion, the (UCl/sub 6/)/sup 2/minus// ion, and (UO/sub 2/Cl/sub 2/(OH/sub 2/)/sub 3/). The neutral moiety crystallizes as a hydrogen-bonded crown ether complex; however, crown ether complexation of amore » counterion, either an ammonium ion formed during the oxidation of U(IV) or a Na/sup +/ ion leached from glass reaction vessels, resulted in novel crystalline complexes of the ionic species. ((NH/sub 4/)(15-crown-5)/sub 2/)/sub 2/(UO/sub 2/Cl/sub 4/) /times/ 2CH/sub 3/CN, ((NH/sub 4/)(benzo-15-crown-5)/sub 2/)/sub 2/(UCl/sub 6/) /times/ 4CH/sub 3/CN, and ((NH/sub 4/)(dibenzo-18-crown-6))/sub 2/(UO/sub 2/Cl/sub 4/) /times/ 2CH/sub 3/CN have been structurally characterized by single-crystal X-ray diffraction techniques. The results of all the crystal studies are presented in detail. The ammonium ions interact with the crown ethers via hydrogen-bonding and electrostatic interactions. 15-Crown-5 and benzo-15-crown-5 form 2:1 sandwich cations, allowing no H/sub 4/N/sup +//hor ellipsis/(UO/sub 2/Cl/sub 4/)/sup 2/minus// interaction. The dibenzo-18-crown-6 complexed ammonium ions are 1:1 and form bifurcated hydrogen bonds with the chlorine atoms in the (UO/sub 2/Cl/sub 4/)/sup /minus// anion. The formation of (Na(12-crown-4)/sub 2//sub 2/(UO/sub 2/Cl/sub 4/) /times/ 2OHMe and (UO/sub 2/Cl/sub 2/(OH)/sub 2/)/sub 3/) /times/ 18-crown-6 /times/ H/sub 2/O /times/ OHMe has been confirmed by preliminary single-crystal X-ray diffraction studies.« less
  • The chemistry of novel polyhedral borane derivatives has recently attracted new interest because of their potential application in the liposome-mediated boron neutron capture therapy (BNCT) of cancer. The [trans-B{sub 20}H{sub 18}]{sup 2{minus}} polyhedral borane anion has been found to be a versatile source for a variety of these boron-rich derivatives. The synthesis of the stereochemically unprecedented [cis-B{sub 20}H{sub 18}]{sup 2{minus}} and the ammonio-substituted anion [cis-B{sub 20}H{sub 17}NH{sub 3}]{sup {minus}} ([2]{sup {minus}}) has been reported. The two three-center two-electron bonds of [2]{sup {minus}} are electron deficient and susceptible to nucleophilic attack, and the reaction of [2]{sup {minus}} with hydroxide ion producedmore » disubstituted [{alpha}{sup 2}-B{sub 20}H{sub 16}NH{sub 3}(OH)]{sup 3{minus}}. A recent investigation of the reaction of [2]{sup {minus}} with liquid ammonia has led to the discovery of the diammonio-substituted anion, [{alpha}{sup 2}-B{sub 20}H{sub 16}(NH{sub 3}){sub 2}]{sup 2{minus}}. Subsequent aqueous ferric ion oxidation resulted in the neutral derivative, trans-B{sub 20}H{sub 16}(NH{sub 3}){sub 2}. They report here the syntheses and structures of the anion and the neutral compound.« less