Glycerol 3-phosphate Cytidylyltransferase Ashley Mericle

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Transcript of Glycerol 3-phosphate Cytidylyltransferase Ashley Mericle

  • Slide 1
  • Glycerol 3-phosphate Cytidylyltransferase Ashley Mericle
  • Slide 2
  • Sequence
  • Slide 3
  • Overall Structure
  • Slide 4
  • Structure 5 parallel sheets -helices pack next to the sheets Form / supersecondary structure 3 10 helices connect the sheets
  • Slide 5
  • Function Teichoic acids are major componenets of the cell walls of most Gram-positive bacteria. The genes concerned with the synthesis of poly(glycerol phosphate) are organized into two operons. The gene of the tagDEF operon, tagD, encodes glycerol-3-phosphate cytidylyltransferase. It catalyzes the transfer of the cytidyl group of CTP to glycerol phosphate.
  • Slide 6
  • Teichoic Acid Production Pathway
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  • Overall Reaction V max : 55.1 8.3 mol/min/mg K m : 1.4 0.1 Glycerol 3-phosphate Cytidine 5-triphosphate (CTP)Cytidine diphosphoglycerol (CDP-glycerol)
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  • Important Amino Acids Lysine 44 Lysine 46
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  • Dimer Interface Arginine 63 is buried From one of the conserved sequences Tryptophan 15 Leucine12 and Leucine 13 hydrophobic
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  • Interface Amino Acids Leucine 12 Leucine 13 Tryptophan 15
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  • Helical Wheels of Interface Helices
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  • Active Site Residues that interact with CTP do not extend across the dimer interface. This suggests each chain possesses its own active site There is the possibility for interaction between them due to the conserved residues The active site is shaped like a bowl and is open to solvent at its top.
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  • Active Site
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  • Sequence Alignment
  • Slide 15
  • Conserved Residues GX(Y/F)DXXHXGH RTXGISTT RYVDEVI The first two conserved sequences comprise one side of the active site bowl.
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  • Medical Relevance Some bacteria, which are normally found in the mouth, digestive tract, urinary tract, and upper airways of the respiratory system can cause endocarditis. If the bacteria get in the bloodstream, it can get to the heart and cause inflammation in the heart lining. It is thought that if the reaction involving GCT can be stopped, then the production of infected heart lining can be stopped.
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  • References Pattridge KA, Weber CH, Friesen JA, Sanker S, Kent C, Ludwig ML. (2003) J Biol Chem. 278, 51863-51871 Weber CH, Park YS, Sanker S, Kent C, Ludwig ML. (1999) Structure Fold Des. 7, 1113-1124.